Marıa Forray - Academia.edu (original) (raw)

Papers by Marıa Forray

Research paper thumbnail of Regulation of excitatory amino acid release by N-methyl-d-aspartate receptors in rat striatum: in vivo microdialysis studies

Brain Research, Jul 1, 1992

The microdialysis technique was utilized to study the effects of N-methyI-D-as~,:lrtate (NMDA) re... more The microdialysis technique was utilized to study the effects of N-methyI-D-as~,:lrtate (NMDA) receptor ligands on the in vivo release of endogenous glutamate (Glu) and aspartate (Asp) from the rat striatum. Addition of NMDA (250 and 500/zM) to the dialysis perfusion solution resulted in a striking dose-dependent increase in extracellular concentrations of Glu and Asp in the striatum. The NMDA-induced effects were reduced in a dose-related way by prior perfusion with 75 ~M dizocilpine (MK-801), a non-competitive NMDA receptor antagonist. MK-801, at 75 p.M, produced no changes on basal levels of Glu and Asp. However, 100/zM MK-801 did increase Glu and Asp extracellular concentrations. Local infusion with 500 ~M D-serine, an agonist at the glycine site associated to the NMDA receptor, significantly increased basal level of Glu, but not Asp. Such D-serine-induced effects were reduced by 7-CI-kynurenic acid (200 ~.M), a selective blocker of the glycine site present in the NMDA receptor, it is proposed that activation of NMDA receptors by endogenous Glu and Asp enhances the subsequent release of these excitatory amino acids in the striatum. Part of these NMDA receptors might be located presynaptically on cortico-striatal nerve endings. In addition, postsynaptic NMDA receptors present in the striatum may also indirectly modulate the release of Glu and Asp, through trans-synaptic mechanism,

Research paper thumbnail of Augmentation of the behavioural effects of desipramine by repeated immobilization stress

Behavioural Brain Research, Dec 1, 2010

The present report provides evidence that repeated immobilization stress (RIS) induced a noradren... more The present report provides evidence that repeated immobilization stress (RIS) induced a noradrenergicdependent depressive-like behaviour and an augmented behavioural response to desipramine (DMI), a noradrenaline reuptake inhibitor (NRI), in the forced swimming test (FST). The present results show that RIS decreased the baseline of climbing behaviour in the FST. Whereas subchronic administration of DMI (10 mg/kg, three times in a 24 h period) induced a significantly higher increase in climbing behaviour on repeatedly stressed rats compared to controls. The results also show that the concomitant administration of the low dose of DMI (3 mg/Kg) during the RIS fully prevented the decrease of climbing behaviour induced by RIS, without exerting behavioural effects in control rats, further supporting an augmented response to the DMI antidepressant effects in the repeatedly stressed rats. In conclusion, our data indicate that RIS not only changes the behavioural responses in the FST but also increases the antidepressant effects of DMI.

Research paper thumbnail of Modulation of dendritic release of dopamine by metabotropic glutamate receptors in rat substantia nigra

Biochemical Pharmacology, Apr 1, 2002

A superfusion system was used to study the effects of metabotropic glutamate receptor (mGluR) lig... more A superfusion system was used to study the effects of metabotropic glutamate receptor (mGluR) ligands upon the release of [(3)H]dopamine ([(3)H]DA) previously taken up by rat substantia nigra (SN) slices. trans-(+/-)-1-Amino-(1S,3R)-cyclopentane dicarboxylic acid (trans-ACPD; 100 and 600 microM), a group I and II mGluR agonist, evoked the release of [(3)H]DA from nigral slices. This last effect was reduced significantly by (2S,3S,4S)-2-methyl-2-(carboxycyclopropyl)-glycine (MCCG; 300 microM), an antagonist of group II mGluR, or by the addition of tetrodotoxin (D-APV; 1 microM) to the superfusion medium. D-(-)-2-Amino-5-phosphono-valeric acid (100 microM), an N-methyl-D-aspartate receptor antagonist, or the presence of Mg(2+) (1.2mM) in the superfusion medium did not modify trans-ACPD-induced [(3)H]DA release. In addition, a group II mGluR agonist such as (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)-glycine (DCG-IV; 100 microM) significantly induced the release of [(3)H]DA from nigral slices, whereas a group I mGluR agonist such as (RS)-3,5-dihydroxyphenylglycine (DHPG; 50 and 100 microM) did not modify the release of the [(3)H]-amine. Further experiments showed that the NMDA (100 microM)-evoked release of [(3)H]DA was decreased significantly by prior exposure of SN slices to trans-ACPD. Finally, partial denervation of the DA nigro-striatal pathway with 6-hydroxydopamine (6-OH-DA) increased trans-ACPD-induced release of [(3)H]DA, whereas it decreased trans-ACPD inhibitory effects on NMDA-evoked release of [(3)H]DA from nigral slices. The present results suggest that the dendritic release of DA in the SN is regulated by mGluR activation. Such nigral mGluR activation may produce opposite effects upon basal and NMDA-evoked release of DA in the SN. In addition, such mGluR-induced effects in the SN are modified in response to partial denervation of the DA nigro-striatal pathway.

Research paper thumbnail of Adrenalectomy decreases corticotropin-releasing hormone gene expression and increases noradrenaline and dopamine extracellular levels in the rat lateral bed nucleus of the stria terminalis

Journal of Neuroscience Research, 2005

The bed nucleus of the stria terminalis (BNST) has a high density of corticotropin-releasing horm... more The bed nucleus of the stria terminalis (BNST) has a high density of corticotropin-releasing hormone (CRH)-containing neurons that are significantly innervated by noradrenergic and dopaminergic nerve terminals. This limbic structure is involved in the extrahypothalamic response to stress. The purpose of the present work is to study whether the absence of glucocorticoids, induced by a long-term adrenalectomy, regulates CRH gene expression and noradrenaline and dopamine extracellular levels in the rat BNST. The results showed that adrenalectomy decreases CRH mRNA in the dorsal lateral BNST but not in the ventral lateral BNST. Adrenalectomy also decreases CRH-like immunoreactivity both in BNST subnuclei and in the central nucleus of the amygdala. In addition, adrenalectomy significantly increases noradrenaline and dopamine extracellular levels in the lateral BNST. The present results suggest that adrenalectomy regulates CRH gene expression and noradrenaline and dopamine extracellular levels in the BNST in an opposite way. Thus, the present study adds novel evidence further supporting that the BNST and the central nucleus of the amygdala form part of an adrenal steroid-sensitive extrahypothalamic circuit that has been involved in fear and anxiety responses and in clinical syndromes such as melancholic depression, posttraumatic stress disorders, and addiction.

Research paper thumbnail of Corticotropin-releasing hormone and urocortin: redundant or distinctive functions?

Brain Research Reviews, Dec 1, 2004

Neuropeptides play important roles in synaptic transmission. Among them, the peptides of the cort... more Neuropeptides play important roles in synaptic transmission. Among them, the peptides of the corticotropin-releasing hormone (CRH) family present interesting features. The two main mammalian peptides of this family, CRH and urocortin (UCN), signal through the same receptors, CRH-R1 and CRH-R2. The question arises as to whether these peptides have redundant or distinctive functions. The fact that CRH and UCN have high affinity for both receptors has hampered the possibility to define the functional contribution of each peptide. Recent studies conducted on mice deficient in CRH, CRH-R1, CRH-R2 and CRH-R1/CRH-R2, as well as in two different UCN-deficient mice, have added relevant information towards the understanding of the role of this peptide family in the CNS. Our new anatomical evidence of UCN expression in the septum will be discussed in this context.

Research paper thumbnail of Role of noradrenergic projections to the bed nucleus of the stria terminalis in the regulation of the hypothalamic–pituitary–adrenal axis

Brain Research Reviews, Dec 1, 2004

The bed nucleus of the stria terminalis (BNST) plays an important role in the regulation of the h... more The bed nucleus of the stria terminalis (BNST) plays an important role in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis during stress and it is a major extrahypothalamic relay to the paraventricular nucleus of the hypothalamus (PVN) from the amygdala and the hippocampus. In this review, we discuss the anatomical, neurochemical and behavioral evidence that substantiate a role for noradrenergic terminals of the anterior BNST in the regulation of the HPA axis. We propose the hypothesis that BNST noradrenaline (NA) participates in the regulation of the hippocampal inhibitory influence on the HPA axis activation. The observation that NA exerts a tonic inhibitory effect upon glutamatergic transmission in the anterior BNST supports this hypothesis. We also discuss the known mechanisms involved in the regulation of BNST NA extracellular levels and the possible interactions between NA and corticotropin-releasing hormone (CRH), and of CRH with glutamate (GLU) in the regulation of the HPA axis activity exerted by the BNST. The evidence discussed in the present review situates the BNST as a key extrahypothalamic center that relays and integrates limbic and autonomic information related to stress responses suggesting that dysregulation in the functioning of the BNST may underlie the pathophysiology of stress-related psychiatric disorders.

Research paper thumbnail of Noradrenaline inhibits glutamate release in the rat bed nucleus of the stria terminalis: In vivo microdialysis studies

Journal of Neuroscience Research, Feb 1, 1999

The microdialysis technique was used to simultaneously study the in vivo extracellular levels of ... more The microdialysis technique was used to simultaneously study the in vivo extracellular levels of noradrenaline, glutamate, and gamma aminobutyric acid (GABA) in the bed nucleus of the stria terminalis in order to assess the regulation that noradrenaline may exert upon the release of amino acid neurotransmitters. Perfusion through the probe with UK14304, a selective alpha2-adrenergic agonist, produced a significant decrease of noradrenaline and glutamate extracellular levels. Perfusion through the probe with RX821002, a selective alpha2-adrenergic antagonist, produced a significant increase of noradrenaline and glutamate basal extracellular levels. Perfusion with prazosine, a selective alpha1-adrenergic antagonist, produced a significant decrease of noradrenaline basal extracellular levels without affecting glutamate levels. Under the same conditions, GABA basal extracellular levels were not changed in the presence of any of the alpha-adrenergic ligands studied. The perfusion of high potassium through the probe induced a significant Ca++dependent release of the three neurotransmitters; however, extracellular noradrenaline returned to normal levels even though potassium was still present. In addition, it was observed that alpha-adrenergic receptor ligands exerted differential effects upon K+-induced release of noradrenaline and glutamate. Perfusion with the nonselective alpha-adrenergic antagonist, phenoxybenzamine, presented a biphasic effect upon K+-induced release of noradrenaline; a significant decrease during the first 5 min of stimulation followed by a significant increase in the next 5 min of stimulation. Perfusion with RX821002 produced a significant increase in K+-induced release of noradrenaline that returned to normal basal values before the end of the stimulation period. In contrast, local perfusion with prazosine caused a significant decrease of K+-induced noradrenaline release. In the case of glutamate, perfusion through the probe with phenoxybenzamine produced a significant increase in K+-induced release of glutamate. In addition, RX821002 and prazosine produced a significant increase in K+-induced release of glutamate. Perfusion through the probe with UK14304 produced a significant decrease of both noradrenaline and glutamate K+-induced release. The present results show that noradrenaline in the bed nucleus of stria terminalis exerts a significant inhibition over its own release through alpha2-adrenergic receptors and over glutamate release mainly through alpha2-adrenergic receptors. Thus, the results suggest that noradrenaline in the bed nucleus of the stria terminalis maintains an inhibitory tone over the information flow mediated by glutamate.

Research paper thumbnail of Non-neuronal endogenous GABA efflux from the rat oviduct

Research paper thumbnail of 8-oxoguanine DNA glycosylase, but not Kin17 protein, is translocated and differentially regulated by estrogens in rat brain cells

Neuroscience, 2005

8-oxoguanine DNA glycosylase and Kin17 are proteins widely distributed and phylogenetically conse... more 8-oxoguanine DNA glycosylase and Kin17 are proteins widely distributed and phylogenetically conserved in the CNS. 8-oxoguanine DNA glycosylase is a DNA repair enzyme that excises 7,8-dihydro-8-oxoguanine present in DNA damaged by oxidative stress. Kin17 protein is involved in DNA repair and illegitimate recombination in eukaryotic cells. The present study evaluates the effect of ovarian hormones on the expression of both proteins in the magnocellular paraventricular nucleus of the hypothalamus and the bed nucleus of the stria terminalis in female and male rat brains. In the paraventricular nucleus, ovariectomy induced a significant decrease in the number of 8-oxoguanine DNA glycosylase-positive nuclei as well as in their relative fluorescent intensity as compared with ovariectomized-estradiol treated and proestrous groups. Confocal microscopy observation demonstrated that oxoguanine DNA glycosylase protein is located in the Hoechst-dyed nuclei and cytoplasm in male and ovariectomized rats. Surprisingly, following estradiol administration to ovariectomized and proestrous rats, the 8-oxoguanine DNA glycosylase immunolabeling was observed in the nucleolus, the cytoplasm and the dendrites of cells, while Kin17 protein was always localized in the cell nuclei. In the bed nucleus of the stria terminalis, the number of 8-oxoguanine DNA glycosylase-positive nuclei during proestrous was significantly lower than the number obtained in males and ovariectomized rats and similar to the number of ovariectomized-estradiol-treated groups. In contrast to these observations, no significant differences were observed in the expression of kin17 protein. Our results suggest that estrogens differentially regulate the expression of 8-oxoguanine DNA glycosylase, but not that of Kin17 protein, in specific regions of the rat brain and that estradiol can translocate the 8-oxoguanine DNA glycosylase protein within nuclei and to other subcellular compartments.

Research paper thumbnail of Natural expression of immature Ucn antisense RNA in the rat brain. Evidence favoring bidirectional transcription of the Ucn gene locus

Molecular Brain Research, Sep 1, 2005

Recently, it has been shown the endogenous expression of an antisense urocortin (Ucn) transcript ... more Recently, it has been shown the endogenous expression of an antisense urocortin (Ucn) transcript in the rat brain and other tissues. In the present work, by means of two complementary techniques, specific-strand RT-PCR and in situ hybridization, we showed the natural expression of a second novel antisense Ucn RNA of higher size. Specific-strand RT-PCR of total RNA, cloning and sequence analysis together with the different subcellular localization observed for both antisense Ucn RNAs indicated that this novel antisense Ucn transcript corresponded to the immature form of the previously described antisense Ucn RNA. Sequence analysis indicated that this immature antisense Ucn transcript uses non-consensus CT-AC splice sites, exactly complementary to its sense counterpart. The mature antisense Ucn transcript was also amplified after specific-strand RT-PCR of poly(A)-RNA, suggesting that the mature antisense Ucn transcript is polyadenylated. We also proved that the region complementary to the promoter of sense Ucn RNA, including the TATA box, is part of the antisense Ucn RNA. Finally, we showed that the region complementary to the 3'-end of Ucn mRNA behaves as a functional promoter for the transcription of antisense Ucn RNA. Thus, the results indicate that the 3'-ends of both sense and antisense Ucn RNAs are the only non-complementary sequences between them. In conclusion, the present findings suggest that the Ucn gene locus naturally undergoes bidirectional transcription yielding a sense and an antisense RNA expanding the spectrum of antisense RNAs originated from the same genomic loci to antisense transcripts that are spliced using these non-consensus CT-AC splice sites.

Research paper thumbnail of Regulation of norepinephrine release from the rat bed nucleus of the stria terminalis: In vivo microdialysis studies

Journal of Neuroscience Research, Dec 15, 1997

The microdialysis technique was used to study the in vivo extracellular levels of norepinephrine ... more The microdialysis technique was used to study the in vivo extracellular levels of norepinephrine in the bed nucleus of the stria terminalis. A basal level of 2.34 +/-0.25 fmol/microl of norepinephrine was observed. Desipramine (2 and 10 microM), a norepinephrine uptake blocker, significantly increased extracellular levels of norepinephrine. Reversed perfusion with high potassium in the presence of 2 microM desipramine induced the release of norepinephrine. Instead, in the presence of 10 microM desipramine, a significant decrease in the induced release of norepinephrine was observed. Clonidine, an alpha2-adrenergic agonist, significantly decreased basal extracellular levels of norepinephrine and the K+-induced release of norepinephrine. In contrast, yohimbine and RX821002, two alpha2-adrenergic antagonists, significantly increased basal extracellular levels of norepinephrine but not the release of norepinephrine induced by 70 mM K+. Perfusion of tetrodotoxin through the probe located in the bed nucleus of the stria terminalis significantly decreased both the basal extracellular level and the K+-induced release of norepinephrine. Furthermore, perfusion of tetrodotoxin through a microdialysis probe implanted in the medial forebrain bundle also decreased basal extracellular levels of norepinephrine in the bed nucleus of the stria terminalis. The results show that in vivo there is a significant noradrenergic tonic activity in the bed nucleus of the stria terminalis. This tonic activity depends on the impulse flow through medial forebrain bundle nerve fibers. Under these conditions, extracellular levels of norepinephrine in the bed nucleus of the stria terminalis are regulated by the magnitude of norepinephrine uptake and by presynaptic alpha2-adrenergic receptors.

Research paper thumbnail of Desipramine prevents the sustained increase in corticotropin-releasing hormone-like immunoreactivity induced by repeated immobilization stress in the rat central extended amygdala

Journal of Neuroscience Research, 2006

Clinical and experimental studies have shown that the activation of corticotropin-releasing hormo... more Clinical and experimental studies have shown that the activation of corticotropin-releasing hormone (CRH) and noradrenergic systems mediate stress-induced anxiety. Repeated immobilization stress (RIS) has been shown to induce longlasting anxiety behavior and changes in noradrenaline turnover. The present work was aimed at studying the effect of RIS on the in situ expression of CRH-LI in the central extended amygdala and paraventricular nucleus of the hypothalamus (PVN). Our results showed that RIS for 15 days induces a significant increase of CRH-LI expression in the central extended amygdala. The increase in CRH-LI expression in the central extended amygdala was sustained even after a 25-day stress-free period. The concomitant administration of desipramine (DMI), a specific noradrenaline uptake inhibitor, fully prevented the RIS-induced increase in CRH expression. RIS also induced an increase of CRH-LI expression in the PVN that was prevented by the concomitant DMI administration. In contrast to the sustained effect observed in the central extended amygdala, the RIS-induced increase of CRH-LI expression in the PVN was nonlasting. DMI administration also prevented the RISinduced increase of adrenal gland weight. The present findings showing that RIS induces a sustained increase of CRH expression in the central extended amygdala suggest that the repeated activation of CRH neurons and CRH receptors in the central extended amygdala may underlie the longlasting anxiety behavior induced by RIS. Further studies should address the mechanisms involved in the effect of DMI and its eventual relevance in the therapeutic actions of DMI. V

Research paper thumbnail of Chronic Morphine Treatment and Withdrawal Increase Extracellular Levels of Norepinephrine in the Rat Bed Nucleus of the Stria Terminalis

Journal of Neurochemistry, Jan 4, 2002

Extracellular levels of norepinephrine (NE) and glutamate (Glu) in the ventral bed nucleus of the... more Extracellular levels of norepinephrine (NE) and glutamate (Glu) in the ventral bed nucleus of the stria terminalis (vBNST) of saline-and chronic morphine-treated rats, with or without withdrawal, were studied by means of the in vivo microdialysis technique in anesthetized rats. In addition, the tissue concentration of NE was studied at different rostrocaudal levels of the vBNST. Chronic morphine treatment significantly increased extracellular levels of NE, but not Glu, in vBNST. At 48 h after naloxone-induced morphine withdrawal there was a further significant increase in the extracellular levels of NE, but not Glu, in vBNST. The presence of UK 14304, an ␣ 2-adrenergic agonist, induced a significant decrease in NE extracellular levels in all experimental groups. In contrast, UK 14304 induced a significant decrease in Glu extracellular levels only in saline-treated rats. The results also show that the vBNST presents a rostrocaudal gradient of NE and contains 9.4% of total brain NE. The increase in NE extracellular levels in vBNST induced by chronic morphine treatment and the further increase in NE levels 48 h after naloxone-induced morphine withdrawal suggest that NE in vBNST may be involved in the pharmacological effects of chronic morphine and withdrawal.

Research paper thumbnail of Changes of norepinephrine levels and release in rat cerebral cortex during the estrous cycle

Neuroreport, Dec 1, 1991

We studied the influence of the estrous cycle and ovariectomy on the noradrenergic innervation of... more We studied the influence of the estrous cycle and ovariectomy on the noradrenergic innervation of the rat cerebral cortex. The lowest norepinephrine (NE) concentration was found during estrus in frontal and occipital cortex. At that stage and at diestrus-2, 20 mM K+ induced the lowest release of [3H]NE from occipital region slices, and the highest release was found at 60 mM K+. Ovariectomy (7 days) decreased the 20 mM K+ effect. Yohimbine (10 x 10(-6) M) increased the induced NE release through the cycle but its effects disappeared after ovariectomy. In the frontal cortex the drug effect was only found at diestrus-1 and no changes were observed in the K+ effect through the cycle. Results suggest that normal endocrine influences can modify noradrenergic neurotransmission in the rat cerebral cortex.

Research paper thumbnail of Differential regulation of urocortin mRNA expression in septum and paraventricular nucleus of the hypothalamus of female rats

The Society for Neuroscience Abstracts, 2000

Research paper thumbnail of Effort Displayed During Appetitive Phase of Feeding Behavior Requires Infralimbic Cortex Activity and Histamine H1 Receptor Signaling

Frontiers in Neuroscience, 2019

Research paper thumbnail of Enduring attenuation of norepinephrine synaptic availability and augmentation of the pharmacological and behavioral effects of desipramine by repeated immobilization stress

Neuropharmacology, 2017

Here we provide evidence that repeated immobilization stress (RIS) in rats induces a persistent i... more Here we provide evidence that repeated immobilization stress (RIS) in rats induces a persistent increase in noradrenergic activity in the anterior aspects of the anterolateral bed nucleus of the stria terminalis (alBNST). This increase in noradrenergic activity results from both enhanced synthesis and reuptake of norepinephrine (NE). It leads to a decrease in the synaptic availability of NE, which elicits an augmented noradrenergic response to the inhibitors of NE reuptake (NRIs), such as desipramine (DMI), an antidepressant. The enduring depression-like behavior and the augmentation of the climbing behavior seen in repeatedly stressed rats following subchronic administration of DMI in the forced swimming test (FST) might be explained by a dysregulation of noradrenergic transmission observed in alBNST. Taken together, we propose that dysregulation of noradrenergic transmission such as the one described in the present work may represent a mechanism underlying major depressive disorders (MDD) with melancholic features in humans.

Research paper thumbnail of Infralimbic cortex activation and motivated arousal induce histamine release

Behavioural Pharmacology, 2015

Appetitive behaviours occur in a state of behavioural and physiological activation that allows th... more Appetitive behaviours occur in a state of behavioural and physiological activation that allows the optimal performance of these goal-directed behaviours. Here, we tested the hypothesis that histamine neurons under the command of the infralimbic cortex are important to provide behavioural activation. Extracellular histamine and serotonin were measured by microdialysis of the medial prefrontal cortex in behaving rats in parallel with a picrotoxin microinjection into the infralimbic cortex. The injection aroused the rats behaviourally, increased histamine release and decreased serotonin levels. Inhibition of the infralimbic cortex with muscimol produced the opposite effects on neurotransmitter release. The behavioural activation induced by motivating hungry rats with caged food was paralleled by an immediate histamine release, whereas awakening induced by tapping their microdialysis bowl increased serotonin, but not histamine levels. In conclusion, picrotoxin injection into the infralimbic cortex produces behavioural activation together with histamine release; in a similar manner, induction of an appetitive state produced histamine release, likely related to increased behavioural activation characteristic of an appetitive behaviour.

Research paper thumbnail of Activation of GABA-B receptors induced by systemic amphetamine abolishes dopamine release in the rat lateral septum

Journal of Neurochemistry, 2010

The lateral septum is a brain nucleus involved in various mental disorders such as anxiety and dr... more The lateral septum is a brain nucleus involved in various mental disorders such as anxiety and drug addiction. In the present study, we investigated whether systemic amphetamine, known to release dopamine (DA) in nucleus accumbens, will also release DA in lateral septum. Our results show that systemic amphetamine administration (2 mg/kg i.p.) induced a significant increase in DA extracellular levels in nucleus accumbens but not in lateral septum. Interestingly, intralateral septum perfusion of amphetamine through the microdialysis probe induced a significant increase in DA extracellular levels. To test if GABAergic neurotransmission in lateral septum was responsible for inhibiting the release of DA when amphetamine was administered systemically, we perfused a GABA-B selective antagonist (CGP-52432) intra lateral septum. Systemic amphetamine administration induced a significant increase in lateral septum DA release when CGP-52432 was concomitantly superfused. Our results indicate that the systemic administration of amphetamine induces an increase in lateral septum GABA release and the consequent activation of GABA-B receptors counteracting the direct effect of amphetamine on lateral septum DA release.

Research paper thumbnail of Modulation of dendritic release of dopamine by metabotropic glutamate receptors in rat substantia nigra

Biochemical Pharmacology, 2002

A superfusion system was used to study the effects of metabotropic glutamate receptor (mGluR) lig... more A superfusion system was used to study the effects of metabotropic glutamate receptor (mGluR) ligands upon the release of [(3)H]dopamine ([(3)H]DA) previously taken up by rat substantia nigra (SN) slices. trans-(+/-)-1-Amino-(1S,3R)-cyclopentane dicarboxylic acid (trans-ACPD; 100 and 600 microM), a group I and II mGluR agonist, evoked the release of [(3)H]DA from nigral slices. This last effect was reduced significantly by (2S,3S,4S)-2-methyl-2-(carboxycyclopropyl)-glycine (MCCG; 300 microM), an antagonist of group II mGluR, or by the addition of tetrodotoxin (D-APV; 1 microM) to the superfusion medium. D-(-)-2-Amino-5-phosphono-valeric acid (100 microM), an N-methyl-D-aspartate receptor antagonist, or the presence of Mg(2+) (1.2mM) in the superfusion medium did not modify trans-ACPD-induced [(3)H]DA release. In addition, a group II mGluR agonist such as (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)-glycine (DCG-IV; 100 microM) significantly induced the release of [(3)H]DA from nigral slices, whereas a group I mGluR agonist such as (RS)-3,5-dihydroxyphenylglycine (DHPG; 50 and 100 microM) did not modify the release of the [(3)H]-amine. Further experiments showed that the NMDA (100 microM)-evoked release of [(3)H]DA was decreased significantly by prior exposure of SN slices to trans-ACPD. Finally, partial denervation of the DA nigro-striatal pathway with 6-hydroxydopamine (6-OH-DA) increased trans-ACPD-induced release of [(3)H]DA, whereas it decreased trans-ACPD inhibitory effects on NMDA-evoked release of [(3)H]DA from nigral slices. The present results suggest that the dendritic release of DA in the SN is regulated by mGluR activation. Such nigral mGluR activation may produce opposite effects upon basal and NMDA-evoked release of DA in the SN. In addition, such mGluR-induced effects in the SN are modified in response to partial denervation of the DA nigro-striatal pathway.

Research paper thumbnail of Regulation of excitatory amino acid release by N-methyl-d-aspartate receptors in rat striatum: in vivo microdialysis studies

Brain Research, Jul 1, 1992

The microdialysis technique was utilized to study the effects of N-methyI-D-as~,:lrtate (NMDA) re... more The microdialysis technique was utilized to study the effects of N-methyI-D-as~,:lrtate (NMDA) receptor ligands on the in vivo release of endogenous glutamate (Glu) and aspartate (Asp) from the rat striatum. Addition of NMDA (250 and 500/zM) to the dialysis perfusion solution resulted in a striking dose-dependent increase in extracellular concentrations of Glu and Asp in the striatum. The NMDA-induced effects were reduced in a dose-related way by prior perfusion with 75 ~M dizocilpine (MK-801), a non-competitive NMDA receptor antagonist. MK-801, at 75 p.M, produced no changes on basal levels of Glu and Asp. However, 100/zM MK-801 did increase Glu and Asp extracellular concentrations. Local infusion with 500 ~M D-serine, an agonist at the glycine site associated to the NMDA receptor, significantly increased basal level of Glu, but not Asp. Such D-serine-induced effects were reduced by 7-CI-kynurenic acid (200 ~.M), a selective blocker of the glycine site present in the NMDA receptor, it is proposed that activation of NMDA receptors by endogenous Glu and Asp enhances the subsequent release of these excitatory amino acids in the striatum. Part of these NMDA receptors might be located presynaptically on cortico-striatal nerve endings. In addition, postsynaptic NMDA receptors present in the striatum may also indirectly modulate the release of Glu and Asp, through trans-synaptic mechanism,

Research paper thumbnail of Augmentation of the behavioural effects of desipramine by repeated immobilization stress

Behavioural Brain Research, Dec 1, 2010

The present report provides evidence that repeated immobilization stress (RIS) induced a noradren... more The present report provides evidence that repeated immobilization stress (RIS) induced a noradrenergicdependent depressive-like behaviour and an augmented behavioural response to desipramine (DMI), a noradrenaline reuptake inhibitor (NRI), in the forced swimming test (FST). The present results show that RIS decreased the baseline of climbing behaviour in the FST. Whereas subchronic administration of DMI (10 mg/kg, three times in a 24 h period) induced a significantly higher increase in climbing behaviour on repeatedly stressed rats compared to controls. The results also show that the concomitant administration of the low dose of DMI (3 mg/Kg) during the RIS fully prevented the decrease of climbing behaviour induced by RIS, without exerting behavioural effects in control rats, further supporting an augmented response to the DMI antidepressant effects in the repeatedly stressed rats. In conclusion, our data indicate that RIS not only changes the behavioural responses in the FST but also increases the antidepressant effects of DMI.

Research paper thumbnail of Modulation of dendritic release of dopamine by metabotropic glutamate receptors in rat substantia nigra

Biochemical Pharmacology, Apr 1, 2002

A superfusion system was used to study the effects of metabotropic glutamate receptor (mGluR) lig... more A superfusion system was used to study the effects of metabotropic glutamate receptor (mGluR) ligands upon the release of [(3)H]dopamine ([(3)H]DA) previously taken up by rat substantia nigra (SN) slices. trans-(+/-)-1-Amino-(1S,3R)-cyclopentane dicarboxylic acid (trans-ACPD; 100 and 600 microM), a group I and II mGluR agonist, evoked the release of [(3)H]DA from nigral slices. This last effect was reduced significantly by (2S,3S,4S)-2-methyl-2-(carboxycyclopropyl)-glycine (MCCG; 300 microM), an antagonist of group II mGluR, or by the addition of tetrodotoxin (D-APV; 1 microM) to the superfusion medium. D-(-)-2-Amino-5-phosphono-valeric acid (100 microM), an N-methyl-D-aspartate receptor antagonist, or the presence of Mg(2+) (1.2mM) in the superfusion medium did not modify trans-ACPD-induced [(3)H]DA release. In addition, a group II mGluR agonist such as (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)-glycine (DCG-IV; 100 microM) significantly induced the release of [(3)H]DA from nigral slices, whereas a group I mGluR agonist such as (RS)-3,5-dihydroxyphenylglycine (DHPG; 50 and 100 microM) did not modify the release of the [(3)H]-amine. Further experiments showed that the NMDA (100 microM)-evoked release of [(3)H]DA was decreased significantly by prior exposure of SN slices to trans-ACPD. Finally, partial denervation of the DA nigro-striatal pathway with 6-hydroxydopamine (6-OH-DA) increased trans-ACPD-induced release of [(3)H]DA, whereas it decreased trans-ACPD inhibitory effects on NMDA-evoked release of [(3)H]DA from nigral slices. The present results suggest that the dendritic release of DA in the SN is regulated by mGluR activation. Such nigral mGluR activation may produce opposite effects upon basal and NMDA-evoked release of DA in the SN. In addition, such mGluR-induced effects in the SN are modified in response to partial denervation of the DA nigro-striatal pathway.

Research paper thumbnail of Adrenalectomy decreases corticotropin-releasing hormone gene expression and increases noradrenaline and dopamine extracellular levels in the rat lateral bed nucleus of the stria terminalis

Journal of Neuroscience Research, 2005

The bed nucleus of the stria terminalis (BNST) has a high density of corticotropin-releasing horm... more The bed nucleus of the stria terminalis (BNST) has a high density of corticotropin-releasing hormone (CRH)-containing neurons that are significantly innervated by noradrenergic and dopaminergic nerve terminals. This limbic structure is involved in the extrahypothalamic response to stress. The purpose of the present work is to study whether the absence of glucocorticoids, induced by a long-term adrenalectomy, regulates CRH gene expression and noradrenaline and dopamine extracellular levels in the rat BNST. The results showed that adrenalectomy decreases CRH mRNA in the dorsal lateral BNST but not in the ventral lateral BNST. Adrenalectomy also decreases CRH-like immunoreactivity both in BNST subnuclei and in the central nucleus of the amygdala. In addition, adrenalectomy significantly increases noradrenaline and dopamine extracellular levels in the lateral BNST. The present results suggest that adrenalectomy regulates CRH gene expression and noradrenaline and dopamine extracellular levels in the BNST in an opposite way. Thus, the present study adds novel evidence further supporting that the BNST and the central nucleus of the amygdala form part of an adrenal steroid-sensitive extrahypothalamic circuit that has been involved in fear and anxiety responses and in clinical syndromes such as melancholic depression, posttraumatic stress disorders, and addiction.

Research paper thumbnail of Corticotropin-releasing hormone and urocortin: redundant or distinctive functions?

Brain Research Reviews, Dec 1, 2004

Neuropeptides play important roles in synaptic transmission. Among them, the peptides of the cort... more Neuropeptides play important roles in synaptic transmission. Among them, the peptides of the corticotropin-releasing hormone (CRH) family present interesting features. The two main mammalian peptides of this family, CRH and urocortin (UCN), signal through the same receptors, CRH-R1 and CRH-R2. The question arises as to whether these peptides have redundant or distinctive functions. The fact that CRH and UCN have high affinity for both receptors has hampered the possibility to define the functional contribution of each peptide. Recent studies conducted on mice deficient in CRH, CRH-R1, CRH-R2 and CRH-R1/CRH-R2, as well as in two different UCN-deficient mice, have added relevant information towards the understanding of the role of this peptide family in the CNS. Our new anatomical evidence of UCN expression in the septum will be discussed in this context.

Research paper thumbnail of Role of noradrenergic projections to the bed nucleus of the stria terminalis in the regulation of the hypothalamic–pituitary–adrenal axis

Brain Research Reviews, Dec 1, 2004

The bed nucleus of the stria terminalis (BNST) plays an important role in the regulation of the h... more The bed nucleus of the stria terminalis (BNST) plays an important role in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis during stress and it is a major extrahypothalamic relay to the paraventricular nucleus of the hypothalamus (PVN) from the amygdala and the hippocampus. In this review, we discuss the anatomical, neurochemical and behavioral evidence that substantiate a role for noradrenergic terminals of the anterior BNST in the regulation of the HPA axis. We propose the hypothesis that BNST noradrenaline (NA) participates in the regulation of the hippocampal inhibitory influence on the HPA axis activation. The observation that NA exerts a tonic inhibitory effect upon glutamatergic transmission in the anterior BNST supports this hypothesis. We also discuss the known mechanisms involved in the regulation of BNST NA extracellular levels and the possible interactions between NA and corticotropin-releasing hormone (CRH), and of CRH with glutamate (GLU) in the regulation of the HPA axis activity exerted by the BNST. The evidence discussed in the present review situates the BNST as a key extrahypothalamic center that relays and integrates limbic and autonomic information related to stress responses suggesting that dysregulation in the functioning of the BNST may underlie the pathophysiology of stress-related psychiatric disorders.

Research paper thumbnail of Noradrenaline inhibits glutamate release in the rat bed nucleus of the stria terminalis: In vivo microdialysis studies

Journal of Neuroscience Research, Feb 1, 1999

The microdialysis technique was used to simultaneously study the in vivo extracellular levels of ... more The microdialysis technique was used to simultaneously study the in vivo extracellular levels of noradrenaline, glutamate, and gamma aminobutyric acid (GABA) in the bed nucleus of the stria terminalis in order to assess the regulation that noradrenaline may exert upon the release of amino acid neurotransmitters. Perfusion through the probe with UK14304, a selective alpha2-adrenergic agonist, produced a significant decrease of noradrenaline and glutamate extracellular levels. Perfusion through the probe with RX821002, a selective alpha2-adrenergic antagonist, produced a significant increase of noradrenaline and glutamate basal extracellular levels. Perfusion with prazosine, a selective alpha1-adrenergic antagonist, produced a significant decrease of noradrenaline basal extracellular levels without affecting glutamate levels. Under the same conditions, GABA basal extracellular levels were not changed in the presence of any of the alpha-adrenergic ligands studied. The perfusion of high potassium through the probe induced a significant Ca++dependent release of the three neurotransmitters; however, extracellular noradrenaline returned to normal levels even though potassium was still present. In addition, it was observed that alpha-adrenergic receptor ligands exerted differential effects upon K+-induced release of noradrenaline and glutamate. Perfusion with the nonselective alpha-adrenergic antagonist, phenoxybenzamine, presented a biphasic effect upon K+-induced release of noradrenaline; a significant decrease during the first 5 min of stimulation followed by a significant increase in the next 5 min of stimulation. Perfusion with RX821002 produced a significant increase in K+-induced release of noradrenaline that returned to normal basal values before the end of the stimulation period. In contrast, local perfusion with prazosine caused a significant decrease of K+-induced noradrenaline release. In the case of glutamate, perfusion through the probe with phenoxybenzamine produced a significant increase in K+-induced release of glutamate. In addition, RX821002 and prazosine produced a significant increase in K+-induced release of glutamate. Perfusion through the probe with UK14304 produced a significant decrease of both noradrenaline and glutamate K+-induced release. The present results show that noradrenaline in the bed nucleus of stria terminalis exerts a significant inhibition over its own release through alpha2-adrenergic receptors and over glutamate release mainly through alpha2-adrenergic receptors. Thus, the results suggest that noradrenaline in the bed nucleus of the stria terminalis maintains an inhibitory tone over the information flow mediated by glutamate.

Research paper thumbnail of Non-neuronal endogenous GABA efflux from the rat oviduct

Research paper thumbnail of 8-oxoguanine DNA glycosylase, but not Kin17 protein, is translocated and differentially regulated by estrogens in rat brain cells

Neuroscience, 2005

8-oxoguanine DNA glycosylase and Kin17 are proteins widely distributed and phylogenetically conse... more 8-oxoguanine DNA glycosylase and Kin17 are proteins widely distributed and phylogenetically conserved in the CNS. 8-oxoguanine DNA glycosylase is a DNA repair enzyme that excises 7,8-dihydro-8-oxoguanine present in DNA damaged by oxidative stress. Kin17 protein is involved in DNA repair and illegitimate recombination in eukaryotic cells. The present study evaluates the effect of ovarian hormones on the expression of both proteins in the magnocellular paraventricular nucleus of the hypothalamus and the bed nucleus of the stria terminalis in female and male rat brains. In the paraventricular nucleus, ovariectomy induced a significant decrease in the number of 8-oxoguanine DNA glycosylase-positive nuclei as well as in their relative fluorescent intensity as compared with ovariectomized-estradiol treated and proestrous groups. Confocal microscopy observation demonstrated that oxoguanine DNA glycosylase protein is located in the Hoechst-dyed nuclei and cytoplasm in male and ovariectomized rats. Surprisingly, following estradiol administration to ovariectomized and proestrous rats, the 8-oxoguanine DNA glycosylase immunolabeling was observed in the nucleolus, the cytoplasm and the dendrites of cells, while Kin17 protein was always localized in the cell nuclei. In the bed nucleus of the stria terminalis, the number of 8-oxoguanine DNA glycosylase-positive nuclei during proestrous was significantly lower than the number obtained in males and ovariectomized rats and similar to the number of ovariectomized-estradiol-treated groups. In contrast to these observations, no significant differences were observed in the expression of kin17 protein. Our results suggest that estrogens differentially regulate the expression of 8-oxoguanine DNA glycosylase, but not that of Kin17 protein, in specific regions of the rat brain and that estradiol can translocate the 8-oxoguanine DNA glycosylase protein within nuclei and to other subcellular compartments.

Research paper thumbnail of Natural expression of immature Ucn antisense RNA in the rat brain. Evidence favoring bidirectional transcription of the Ucn gene locus

Molecular Brain Research, Sep 1, 2005

Recently, it has been shown the endogenous expression of an antisense urocortin (Ucn) transcript ... more Recently, it has been shown the endogenous expression of an antisense urocortin (Ucn) transcript in the rat brain and other tissues. In the present work, by means of two complementary techniques, specific-strand RT-PCR and in situ hybridization, we showed the natural expression of a second novel antisense Ucn RNA of higher size. Specific-strand RT-PCR of total RNA, cloning and sequence analysis together with the different subcellular localization observed for both antisense Ucn RNAs indicated that this novel antisense Ucn transcript corresponded to the immature form of the previously described antisense Ucn RNA. Sequence analysis indicated that this immature antisense Ucn transcript uses non-consensus CT-AC splice sites, exactly complementary to its sense counterpart. The mature antisense Ucn transcript was also amplified after specific-strand RT-PCR of poly(A)-RNA, suggesting that the mature antisense Ucn transcript is polyadenylated. We also proved that the region complementary to the promoter of sense Ucn RNA, including the TATA box, is part of the antisense Ucn RNA. Finally, we showed that the region complementary to the 3'-end of Ucn mRNA behaves as a functional promoter for the transcription of antisense Ucn RNA. Thus, the results indicate that the 3'-ends of both sense and antisense Ucn RNAs are the only non-complementary sequences between them. In conclusion, the present findings suggest that the Ucn gene locus naturally undergoes bidirectional transcription yielding a sense and an antisense RNA expanding the spectrum of antisense RNAs originated from the same genomic loci to antisense transcripts that are spliced using these non-consensus CT-AC splice sites.

Research paper thumbnail of Regulation of norepinephrine release from the rat bed nucleus of the stria terminalis: In vivo microdialysis studies

Journal of Neuroscience Research, Dec 15, 1997

The microdialysis technique was used to study the in vivo extracellular levels of norepinephrine ... more The microdialysis technique was used to study the in vivo extracellular levels of norepinephrine in the bed nucleus of the stria terminalis. A basal level of 2.34 +/-0.25 fmol/microl of norepinephrine was observed. Desipramine (2 and 10 microM), a norepinephrine uptake blocker, significantly increased extracellular levels of norepinephrine. Reversed perfusion with high potassium in the presence of 2 microM desipramine induced the release of norepinephrine. Instead, in the presence of 10 microM desipramine, a significant decrease in the induced release of norepinephrine was observed. Clonidine, an alpha2-adrenergic agonist, significantly decreased basal extracellular levels of norepinephrine and the K+-induced release of norepinephrine. In contrast, yohimbine and RX821002, two alpha2-adrenergic antagonists, significantly increased basal extracellular levels of norepinephrine but not the release of norepinephrine induced by 70 mM K+. Perfusion of tetrodotoxin through the probe located in the bed nucleus of the stria terminalis significantly decreased both the basal extracellular level and the K+-induced release of norepinephrine. Furthermore, perfusion of tetrodotoxin through a microdialysis probe implanted in the medial forebrain bundle also decreased basal extracellular levels of norepinephrine in the bed nucleus of the stria terminalis. The results show that in vivo there is a significant noradrenergic tonic activity in the bed nucleus of the stria terminalis. This tonic activity depends on the impulse flow through medial forebrain bundle nerve fibers. Under these conditions, extracellular levels of norepinephrine in the bed nucleus of the stria terminalis are regulated by the magnitude of norepinephrine uptake and by presynaptic alpha2-adrenergic receptors.

Research paper thumbnail of Desipramine prevents the sustained increase in corticotropin-releasing hormone-like immunoreactivity induced by repeated immobilization stress in the rat central extended amygdala

Journal of Neuroscience Research, 2006

Clinical and experimental studies have shown that the activation of corticotropin-releasing hormo... more Clinical and experimental studies have shown that the activation of corticotropin-releasing hormone (CRH) and noradrenergic systems mediate stress-induced anxiety. Repeated immobilization stress (RIS) has been shown to induce longlasting anxiety behavior and changes in noradrenaline turnover. The present work was aimed at studying the effect of RIS on the in situ expression of CRH-LI in the central extended amygdala and paraventricular nucleus of the hypothalamus (PVN). Our results showed that RIS for 15 days induces a significant increase of CRH-LI expression in the central extended amygdala. The increase in CRH-LI expression in the central extended amygdala was sustained even after a 25-day stress-free period. The concomitant administration of desipramine (DMI), a specific noradrenaline uptake inhibitor, fully prevented the RIS-induced increase in CRH expression. RIS also induced an increase of CRH-LI expression in the PVN that was prevented by the concomitant DMI administration. In contrast to the sustained effect observed in the central extended amygdala, the RIS-induced increase of CRH-LI expression in the PVN was nonlasting. DMI administration also prevented the RISinduced increase of adrenal gland weight. The present findings showing that RIS induces a sustained increase of CRH expression in the central extended amygdala suggest that the repeated activation of CRH neurons and CRH receptors in the central extended amygdala may underlie the longlasting anxiety behavior induced by RIS. Further studies should address the mechanisms involved in the effect of DMI and its eventual relevance in the therapeutic actions of DMI. V

Research paper thumbnail of Chronic Morphine Treatment and Withdrawal Increase Extracellular Levels of Norepinephrine in the Rat Bed Nucleus of the Stria Terminalis

Journal of Neurochemistry, Jan 4, 2002

Extracellular levels of norepinephrine (NE) and glutamate (Glu) in the ventral bed nucleus of the... more Extracellular levels of norepinephrine (NE) and glutamate (Glu) in the ventral bed nucleus of the stria terminalis (vBNST) of saline-and chronic morphine-treated rats, with or without withdrawal, were studied by means of the in vivo microdialysis technique in anesthetized rats. In addition, the tissue concentration of NE was studied at different rostrocaudal levels of the vBNST. Chronic morphine treatment significantly increased extracellular levels of NE, but not Glu, in vBNST. At 48 h after naloxone-induced morphine withdrawal there was a further significant increase in the extracellular levels of NE, but not Glu, in vBNST. The presence of UK 14304, an ␣ 2-adrenergic agonist, induced a significant decrease in NE extracellular levels in all experimental groups. In contrast, UK 14304 induced a significant decrease in Glu extracellular levels only in saline-treated rats. The results also show that the vBNST presents a rostrocaudal gradient of NE and contains 9.4% of total brain NE. The increase in NE extracellular levels in vBNST induced by chronic morphine treatment and the further increase in NE levels 48 h after naloxone-induced morphine withdrawal suggest that NE in vBNST may be involved in the pharmacological effects of chronic morphine and withdrawal.

Research paper thumbnail of Changes of norepinephrine levels and release in rat cerebral cortex during the estrous cycle

Neuroreport, Dec 1, 1991

We studied the influence of the estrous cycle and ovariectomy on the noradrenergic innervation of... more We studied the influence of the estrous cycle and ovariectomy on the noradrenergic innervation of the rat cerebral cortex. The lowest norepinephrine (NE) concentration was found during estrus in frontal and occipital cortex. At that stage and at diestrus-2, 20 mM K+ induced the lowest release of [3H]NE from occipital region slices, and the highest release was found at 60 mM K+. Ovariectomy (7 days) decreased the 20 mM K+ effect. Yohimbine (10 x 10(-6) M) increased the induced NE release through the cycle but its effects disappeared after ovariectomy. In the frontal cortex the drug effect was only found at diestrus-1 and no changes were observed in the K+ effect through the cycle. Results suggest that normal endocrine influences can modify noradrenergic neurotransmission in the rat cerebral cortex.

Research paper thumbnail of Differential regulation of urocortin mRNA expression in septum and paraventricular nucleus of the hypothalamus of female rats

The Society for Neuroscience Abstracts, 2000

Research paper thumbnail of Effort Displayed During Appetitive Phase of Feeding Behavior Requires Infralimbic Cortex Activity and Histamine H1 Receptor Signaling

Frontiers in Neuroscience, 2019

Research paper thumbnail of Enduring attenuation of norepinephrine synaptic availability and augmentation of the pharmacological and behavioral effects of desipramine by repeated immobilization stress

Neuropharmacology, 2017

Here we provide evidence that repeated immobilization stress (RIS) in rats induces a persistent i... more Here we provide evidence that repeated immobilization stress (RIS) in rats induces a persistent increase in noradrenergic activity in the anterior aspects of the anterolateral bed nucleus of the stria terminalis (alBNST). This increase in noradrenergic activity results from both enhanced synthesis and reuptake of norepinephrine (NE). It leads to a decrease in the synaptic availability of NE, which elicits an augmented noradrenergic response to the inhibitors of NE reuptake (NRIs), such as desipramine (DMI), an antidepressant. The enduring depression-like behavior and the augmentation of the climbing behavior seen in repeatedly stressed rats following subchronic administration of DMI in the forced swimming test (FST) might be explained by a dysregulation of noradrenergic transmission observed in alBNST. Taken together, we propose that dysregulation of noradrenergic transmission such as the one described in the present work may represent a mechanism underlying major depressive disorders (MDD) with melancholic features in humans.

Research paper thumbnail of Infralimbic cortex activation and motivated arousal induce histamine release

Behavioural Pharmacology, 2015

Appetitive behaviours occur in a state of behavioural and physiological activation that allows th... more Appetitive behaviours occur in a state of behavioural and physiological activation that allows the optimal performance of these goal-directed behaviours. Here, we tested the hypothesis that histamine neurons under the command of the infralimbic cortex are important to provide behavioural activation. Extracellular histamine and serotonin were measured by microdialysis of the medial prefrontal cortex in behaving rats in parallel with a picrotoxin microinjection into the infralimbic cortex. The injection aroused the rats behaviourally, increased histamine release and decreased serotonin levels. Inhibition of the infralimbic cortex with muscimol produced the opposite effects on neurotransmitter release. The behavioural activation induced by motivating hungry rats with caged food was paralleled by an immediate histamine release, whereas awakening induced by tapping their microdialysis bowl increased serotonin, but not histamine levels. In conclusion, picrotoxin injection into the infralimbic cortex produces behavioural activation together with histamine release; in a similar manner, induction of an appetitive state produced histamine release, likely related to increased behavioural activation characteristic of an appetitive behaviour.

Research paper thumbnail of Activation of GABA-B receptors induced by systemic amphetamine abolishes dopamine release in the rat lateral septum

Journal of Neurochemistry, 2010

The lateral septum is a brain nucleus involved in various mental disorders such as anxiety and dr... more The lateral septum is a brain nucleus involved in various mental disorders such as anxiety and drug addiction. In the present study, we investigated whether systemic amphetamine, known to release dopamine (DA) in nucleus accumbens, will also release DA in lateral septum. Our results show that systemic amphetamine administration (2 mg/kg i.p.) induced a significant increase in DA extracellular levels in nucleus accumbens but not in lateral septum. Interestingly, intralateral septum perfusion of amphetamine through the microdialysis probe induced a significant increase in DA extracellular levels. To test if GABAergic neurotransmission in lateral septum was responsible for inhibiting the release of DA when amphetamine was administered systemically, we perfused a GABA-B selective antagonist (CGP-52432) intra lateral septum. Systemic amphetamine administration induced a significant increase in lateral septum DA release when CGP-52432 was concomitantly superfused. Our results indicate that the systemic administration of amphetamine induces an increase in lateral septum GABA release and the consequent activation of GABA-B receptors counteracting the direct effect of amphetamine on lateral septum DA release.

Research paper thumbnail of Modulation of dendritic release of dopamine by metabotropic glutamate receptors in rat substantia nigra

Biochemical Pharmacology, 2002

A superfusion system was used to study the effects of metabotropic glutamate receptor (mGluR) lig... more A superfusion system was used to study the effects of metabotropic glutamate receptor (mGluR) ligands upon the release of [(3)H]dopamine ([(3)H]DA) previously taken up by rat substantia nigra (SN) slices. trans-(+/-)-1-Amino-(1S,3R)-cyclopentane dicarboxylic acid (trans-ACPD; 100 and 600 microM), a group I and II mGluR agonist, evoked the release of [(3)H]DA from nigral slices. This last effect was reduced significantly by (2S,3S,4S)-2-methyl-2-(carboxycyclopropyl)-glycine (MCCG; 300 microM), an antagonist of group II mGluR, or by the addition of tetrodotoxin (D-APV; 1 microM) to the superfusion medium. D-(-)-2-Amino-5-phosphono-valeric acid (100 microM), an N-methyl-D-aspartate receptor antagonist, or the presence of Mg(2+) (1.2mM) in the superfusion medium did not modify trans-ACPD-induced [(3)H]DA release. In addition, a group II mGluR agonist such as (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)-glycine (DCG-IV; 100 microM) significantly induced the release of [(3)H]DA from nigral slices, whereas a group I mGluR agonist such as (RS)-3,5-dihydroxyphenylglycine (DHPG; 50 and 100 microM) did not modify the release of the [(3)H]-amine. Further experiments showed that the NMDA (100 microM)-evoked release of [(3)H]DA was decreased significantly by prior exposure of SN slices to trans-ACPD. Finally, partial denervation of the DA nigro-striatal pathway with 6-hydroxydopamine (6-OH-DA) increased trans-ACPD-induced release of [(3)H]DA, whereas it decreased trans-ACPD inhibitory effects on NMDA-evoked release of [(3)H]DA from nigral slices. The present results suggest that the dendritic release of DA in the SN is regulated by mGluR activation. Such nigral mGluR activation may produce opposite effects upon basal and NMDA-evoked release of DA in the SN. In addition, such mGluR-induced effects in the SN are modified in response to partial denervation of the DA nigro-striatal pathway.