Activation of GABA-B receptors induced by systemic amphetamine abolishes dopamine release in the rat lateral septum (original) (raw)
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Journal of Neurochemistry, 2010
J. Neurochem. (2010) 114, 1678–1686.J. Neurochem. (2010) 114, 1678–1686.AbstractThe 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.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.
Brain Research, 1998
The role of GABA receptors in regulating the mesolimbic dopamine DA system and drug reinforced behaviors has not been well characterized. Using fast-cyclic voltammetry, the effects of specific GABA receptor modulation on DA release in the nucleus accumbens Ž. Ž. NAcc and heroin self-administration SA behavior was investigated. The GABA agonist muscimol, administered either intravenously A Ž. or directly into the ventral tegmental area VTA , significantly increased DA release in the NAcc in 7 of the 10 rats tested. DA release decreased in the remaining three rats; both effects were blocked by pretreatment with the GABA receptor antagonist bicuculline. In A Ž. contrast, the GABA agonist baclofen decreased, while 2-OH-saclofen a GABA antagonist increased DA release in the NAcc. B B However, when VTA GABA receptors were previously activated or inactivated by microinjections of baclofen or 2-OH-saclofen, B systemic injections of muscimol caused an inhibition of NAcc DA release. These results suggest that GABA receptors may be A Ž. co-localized on both DA neurons and non-DA GABAergic interneurons in the VTA, with the effects of GABA determined by the net A effect of both direct inhibition and indirect disinhibition of DA neurons. Finally, although a DA releaser, muscimol was neither self-administered in drug naive rats, nor did it substitute for heroin in rats previously trained to self-administer heroin, suggesting that GABA receptors appear to play a complex role in mediating drug reinforcement, depending upon the dynamic functional state of A GABA receptors on both tegmental DA and non-DA neurons.
Amphetamine regulation of acetylcholine and γ-aminobutyric acid in nucleus accumbens
Neuroscience, 1992
In situ hybridization histochemistry and/n vivo mierodialysis were combined to study the effect of amphetamine on the expression of choline acetyltransferas¢ and glutamate decarboxylase~7 mRNA and in vivo release of acetylcholine and GABA in rat medial nucleus aceumbens. Differential effects on acetyicholine and GABA neurons by a single challenge injection of amphetamine (1.5 mg/kg, s.c.) were apparent in saline-pretreated and amphetamine-pretreated (same dose, twice daily for the previous seven days) rats. ExtraceUular acetylcholine levels were increased up to 50% over a prolonged period following both single and repeated amphetamine. In contrast, extracellular concentrations of GABA were gradually decreased to half the control values, but only in rats receiving repeated amphetamine. Although the increase of acetylcholine release was not associated with any change in choline acetyltransferase mRNA levels, the number of neurons expressing high levels of glutamate decarboxylase67 mRNA was decreased (28%) following repeated injections.
Withdrawal from chronic amphetamine reduces dopamine transmission in the rat lateral septum
Journal of Neuroscience Research, 2014
The lateral septum (LS) is a brain nucleus implicated in the addictive process. This study investigated whether withdrawal from chronic amphetamine (AMPH) induces alterations in dopamine (DA) transmission within the LS. Male Sprague-Dawley rats were injected with AMPH (2.5 mg/kg i.p.) or saline during 14 days and thereafter subjected to 24 hr or 14 days of withdrawal. After these withdrawal periods, we measured DA extracellular levels by in vivo microdialysis, DA tissue levels, and tyrosine hydroxylase (TH) and vesicular monoamine transporter-2 (VMAT2) expression in the LS. Our results showed a significant decrease in K 1 -induced release of DA in the LS of AMPH-treated rats, 14 days after withdrawal compared with saline-treated rats. There were no significant differences in DA tissue content and TH expression. Interestingly, there was a decrease of LS VMAT2 expression in AMPH-treated rats, 14 days after withdrawal compared with saline-treated rats. This is the first neurochemical evidence showing that withdrawal from repeated AMPH administration decreases K 1 -induced DA release in the rat LS. Our results suggest that this decrease in DA releasability could be due to a decrease in DA vesicular uptake. The possibility that these neurochemical changes are associated with AMPH abstinence syndrome should be further explored. V C 2014 Wiley Periodicals, Inc.
Neuroscience, 2001
AbstractÐWe have previously shown that a large part of the d-amphetamine-induced release of dopamine in the nucleus accumbens is not associated with an increase in locomotor activity, and that ªfunctionalº dopamine release (i.e. release of dopamine associated with locomotor activity) requires the distal facilitation of noradrenergic transmission through a1adrenergic receptors in the prefrontal cortex. To determine the role of monosynaptic or polysynaptic projections from the prefrontal cortex to the nucleus accumbens in these amphetamine responses, either AMPA/kainate (6-cyano-7-nitroquinoxaline-2,3-dione, CNQX, 300 mM), N-methyl-d-aspartate (d(2)-2-amino-5-phosphono-pentanoic acid, APV, 500 mM) or metabotropic [(1)-a-methyl-4-carboxy-phenylglycine, MCPG, 10 mM] glutamate receptor antagonists were infused through a dialysis probe in the rat nucleus accumbens. CNQX and MCPG but not APV reduced the ªnon-functionalº release of dopamine evoked by local (3 mM) and systemic d-amphetamine (2 mg/kg i.p.) treatments. However, the locomotor hyperactivity and functional dopamine release induced by systemic d-amphetamine were abolished by MCPG, but neither by CNQX nor by APV. MCPG treatment also abolished the hyperlocomotor activity and functional dopamine release evoked by bilateral morphine injection into the ventral tegmental area. The dopamine release evoked by this morphine treatment was 16-fold lower than that induced by the systemic d-amphetamine injection, although similar behavioral activations were observed.
Amphetamine-stimulated cortical acetylcholine release: role of the basal forebrain
Brain Research, 2001
Systemic administration of amphetamine results in increases in the release of acetylcholine in the cortex. Basal forebrain mediation of this effect was examined in three experiments using microdialysis in freely-moving rats. Experiment 1 examined whether dopamine receptor activity within the basal forebrain was necessary for amphetamine-induced increase in cortical acetylcholine by examining whether intra-basalis perfusion of dopamine antagonists attenuates this increase. Systemic administration of 2.0 mg / kg amphetamine increased dopamine efflux within the basal forebrain nearly 700% above basal levels. However, the increase in cortical acetylcholine efflux following amphetamine administration was unaffected by intra-basalis perfusions of high concentrations of D1-(100 mM SCH 23390) or D2-like (100 mM sulpiride) dopamine receptor antagonists. Experiments 2 and 3 determined whether glutamatergic or GABAergic local modulation of the excitability of the basal forebrain cholinergic neurons influences the ability of systemic amphetamine to increase cortical acetylcholine efflux. In Experiment 2, perfusion of kynurenate (1.0 mM), a non-selective glutamate receptor antagonist, into the basal forebrain attenuated the increase in cortical acetylcholine produced by amphetamine. Experiment 3 revealed that positive modulation of GABAergic transmission by bilateral intra-basalis infusion of the benzodiazepine receptor agonist chlordiazepoxide (40 mg / hemisphere) also attenuated the amphetamine-stimulated increase in cortical acetylcholine efflux. These data suggest that amphetamine increases cortical acetylcholine release via a complex neuronal network rather than simply increasing basal forebrain D1 or D2 receptor activity.
GABA(B) receptors: altered coupling to G-proteins in rats sensitized to amphetamine
Neuroscience, 2000
Modified dopamine and glutamate neurotransmission in discrete brain regions is implicated in stimulant-induced behavioral sensitization. Release of both neurotransmitters is influenced by GABA(B) metabotropic receptors for the principal inhibitory neurotransmitter GABA. Accordingly, GABA(B) receptors were examined in rats sensitized to amphetamine by measuring receptor density and coupling to G-proteins indicated as [(3)H]baclofen binding and baclofen-mediated [(35)S]GTP gamma S binding. Repeated treatment with (+)-amphetamine (5mg/kg per day, i.p., for five days) sensitized the rats to amphetamine challenge (1mg/kg) at 14 days, but not one day, later. GABA(B) receptor density was not altered at either time. Baclofen-mediated [(35)S]GTP gamma S binding, however, was selectively augmented in the prefrontal cortex and attenuated in the nucleus accumbens at 14 days, but not one day, after amphetamine treatment. Changes in GABA(B) receptor coupling to G-proteins in rats sensitized to am...
Dopamine-GABA interactions in the nucleus accumbens and lateral septum of the rat
Brain Research, 1987
The relationships between dopaminergic afferents and GABAergic neurones were studied at the electron microscopic level in the rat lateral septum and nucleus accumbens by coupling 6-hydroxydopamine degeneration and y-aminobutyric acid (GABA) immunocytochemistry. Degenerating fibres were observed in the two regions making synaptic contact with GABA-immunoreactive and nonlabelled cell bodies and dendrites. It is concluded that dopaminergic afferents to the septum and the nucleus accumbens contact, among others, a population of GABAergic cells. A similar route of regulation of the basalo-cortical and septo-hippocampal cholinergic pathways by dopaminergic afferents is proposed.