A functional effect of dopamine in the nucleus accumbens and in some other dopamine-rich parts of the rat brain (original) (raw)
Related papers
Psychopharmacology, 1988
Lesion studies employing 6-hydroxydopamine (6-OHDA) suggest that locomotor hyperactivity induced by certain stimulant drugs is dependent on dopaminergic neurotransmission in the nucleus accumbens (NACC). However, studies to date have not adequately controlled for the reported effects of 6-OHDA on baseline (non-drug) activity and on DA levels in other terminal regions. Slow bilateral infusions of 6-OHDA into the NACC, but not into olfactory tubercle (OT) or medial prefrontal cortex (mPFCx), reduced d-amphetamine (0.5 mg/kg SC) hyperactivity and resulted in a "supersensitive" (hyperactive) response to a low dose of apomorphine (0.1 mg/kg SC) in photocell cages. Direct observation revealed no behavioral changes in OT lesioned rats challenged with apomorphine which might correspond to a "denervation supersensitivity" syndrome. Assays of DA and 5-hydroxytryptamine (5-HT) in mPFCx, OT, NACC, and caudate-putamen revealed that 6-OHDA infusion into NACC caused substantial DA loss in NACC, OT and mPFCx, whereas infusion at mPFCx or OT sites depleted DA locally (>85% loss) with little or no remote change. Concentrations of 5-HT were little altered by 6-OHDA, except for a local depletion in mPFCx. The present results confirm the importance of nucleus accumbens DA in the expression of locomotor stimulation induced by apomorphine and d-amphetamine, and suggest that the mPFCx and OT do not make an important contribution.
Relationship of Dopamine of the Nucleus Accumbens with Intra-infralimbic Apomorphine Microinjection
Objective(s): The dopamine level of the nucleus accumbens changes during some stereotyped behaviors. To study dopamine level of the nucleus accumbens in intra infralimbic apomorphine-induced climbing, microdialysis probes were implanted into the nucleus accumbens shell of male Sprague Dawley rats weighting 275–400 g. Materials and Methods: The rats were divided into two groups (apomorphine and control) of least eleven rats in each group. Apomorphine at dose of 5 μg/0.5 μl or its vehicle was microinjected into the infralimbic in apomorphine and control groups respectively. Then, changes in dopamine levels in the nucleus accumbens shell were monitored. The concentration of dopamine was measured by High-Performance Liquid Chromatography-Electochemical (HPLC-ECD). Finally, the stereotyped behaviors were recorded. Results: The mean of dopamine levels for all of after microinjection period in control and drug groups were 450% and 150% respectively compared to those of before microinjection period. However, there was no significant difference between groups of apomorphine and control. In addition, the return of dopamine level to the baseline was faster in apomorphine group than the control group. Conclusion: The intra infralimbic apomorphine-induced climbing at dose of 5 μg/0.5 μl was not modulated via the increase of dopamine level in the nucleus accumbens area.
European Journal of Pharmacology, 1991
There is accumulating evidence that some antidepressant treatments can increase the functional output of tile meso-accumbens dopa~ne~c system. For example, chronic ad~~stration of tricyclic ~tidepr~nt drugs such as i~pr~e and desipramine (DMI) enhances the locomotor stimulant effects of d-amphetamine. Subsensiti~ty of inhibitory dopamine (DA) autoreceptors and supersensitivity of postsynaptic DA receptor mechanisms are among the mechanisms that have been suggested to underlie these observations. The present experiments investigated the effects of acute and chronic DMI treatment on interstitial DA concentrations in the nucleus accumbens and striatum using in vivo microdialysis in awake freely moving rats (48 h following implantation of a microdialysis probe). Neither acute (5 mg/kg b.i.d. for 2 days followed by 72 h withdrawal) nor chronic (5 mg/kg b.i.d. for 21 days followed by 72 h ~thdraw~) DMI influenced the ability of a~rno~~ne (25 ag/kg s.c.) to decrease extracellular concentrations of DA or its metabolites 3,4-~~ydroxyphenylacetic acid (DOPAC) and homova~l~c acid (HVA) in the nucleus accumbens. In contrast, d-amphetamine (I.5 mg/kg s.c.)-induced increases in extracellular DA were significantly enhanced in the nucleus accumbens of the chronic but not the acute DMI group. This effect was at least partially regionally selective, as significant effects were not observed in the striatum. In accordance with previous reports, the locomotor stimulant effects of d-amphetamine were also enhanced in the chronic DMI groups. DMI itself failed to alter the interstitial concentrations of DA and its metabolites in the nucleus accumbens of the control and chronic DMI groups. These results provide in vivo neur~he~c~ confi~ation that chronically administered DMI does not produce DA autoreceptor subsensitivity. They also demonstrate that chronic DMI-induced increases in the locomotor stimulant effects of d-amphetamine are accompanied by a selective potentiation of the effects of this stimulant on interstitial DA concentrations in the nucleus accumbens.
Psychopharmacology, 1993
The effects of local injections of dopamine receptor agonists into various areas within the nucleus accumbens or the medial caudate-putamen on the generation of lOcomotor activity were examined. Combinations of 0.32 gg/side of the dopamine receptor agonists SKF 38393 (D1) and quinpirole (D2) produced increases in locomotor activity that varied according to the rostral-caudal placement of the cannulae within the nucleus accumbens. The greatest levels of locomotion were generated by injections into a region in the caudal-central nucleus accumbens, with lower levels of activity elicited by injections into more rostral or caudal regions. A similar pattern of responses was produced by administration of the indirect dopamine agonist d-amphetamine. These results indicate that there is marked heterogeneity in the response of discrete sub-regions of the nucleus accumbens to dopamine receptor stimulation and that this heterogeneity is functionally expressed in the mediation of the locomotor effects of dopaminergic agonists.
Rat genotypes differ in their susceptibility to spontaneously occurring spike-wave discharges and in their dopaminergic properties. In a previous study, it was found that spike-wave discharge incidence decreased in the following order in four rat genotypes during baseline and following injection with the dopamine antagonist haloperidol: apomorphine-suscept-( ) ( ) ible APO-SUS ) WAGr r r r rRij ) apomorphine-unsusceptible APO-UNSUS and ACI rats. The question in the present study was to what extent certain dopaminergic properties are pathognomonic for epileptic rats. Therefore, behavioral responses were assessed in order to investigate the dopaminergic properties in the four rat genotypes. Apomorphineinduced gnawing data imply that the dopamine activity of the nigrostriatal system in the WAGr r r r rRij rats is higher than in APO-SUS but lower than in the ACI and APO-UNSUS rats. Furthermore, in previous studies APO-SUS have been shown to have a higher noveltyr r r r ramphetamine-induced locomotion, indicative of a higher dopamine reactivity of the mesolimbic system as compared to APO-UNSUS rats. Results from the present study showed that WAGr r r r rRij rats have a higher locomotor responsiveness to noveltyr r r r ramphetamine, indicating a higher dopamine reactivity of the mesolimbic system in comparison to the ACI rats. It is suggested that the functional dopaminergic mesolimbic dominance is an important factor in the susceptibility to show spontaneously occurring spike-wave discharges. ᮊ 2001 Lippincott Williams & Wilkins.
Differential responses in central dopaminergic activity induced by apomorphine in IPL nude rat
Behavioural Brain Research, 2002
The IPL nude rat, derived by spontaneous mutation from the Sprague Á/Dawley strain, presents alterations in the prolactin synthesis and secretion due to an increased dopaminergic inhibition. However, there are no reports concerned to central dopamine activity. The corpus striatum is a brain area involved in the development of stereotyped behavior after the activation of mesolimbic and/or nigro-striatal dopamine pathways. In order to identify possible mesolimbic and/or nigro-striatal dysfunctions in the IPL nude rat, we study the spontaneous oral behaviors and the effects of apomorphine-induced dopaminergic activation on stereotyped behavior and neurochemical changes. Males from both strains were injected with saline or apomorphine (2 and 5 mg/kg s.c.) and evaluated during 30 min in a stereotypes oral tests. The corpus striatum and nucleus accumbens were used to measure dopamine (DA), 3,4-dihydroxyphenylalanine (DOPA) and 3,4-dihydroxyphenylacetic acid (DOPAC) by HPLC. The concentrations were expressed as synthesis rate (DA/DOPA) and turnover rate (DOPAC/DA). We observed that the spontaneous gnaw movements were significantly different between the untreated IPL nude and Sprague Á/Dawley (SD) rats. Apomophine injection decreased the amount of stereotyped gnawing in IPL nude rats at the two doses used, but it induced an increase in SD rats. Apomorphine also caused an enhancement in the number of biting and sniffing without modifying the licking behavior. In addition, modifications of the dopaminergic activity were also observed. Synthesis rate in the striatum of IPL nude rats was higher than in SD rats after the injection of saline. Apomorphine caused a reduction of the synthesis rate in both strains. Turnover rate was significantly lower in the striatum of IPL nude rats than in the SD rats injected with saline. Apomorphine caused an increase in the turnover rate in both strains. Contrary to observed in the striatum, the 2 mg/kg dose of apomorphine caused a significant increase in the DA synthesis rate in nucleus accumbens, while 5 mg/kg decrease it in both strains. The DA turnover rate in the same area was lower in IPL nude than in SD rats after saline injection. Apomorphine enhances the DA turnover rate in both strains. We conclude that the modifications of the oral spontaneous and induced stereotypical patterns observed in the IPL nude rats could be related to the differential responses in dopaminergic activity in the two brain areas examined.
Neuroscience, 2005
The selectively bred Roman high-and low-avoidance rats differ in emotionality and responsiveness to the motor effects of acute and repeated psychostimulant administration. These lines also show drastic differences in the neurochemical responses of their mesolimbic dopamine systems to addictive drugs. The nucleus accumbens is critically involved in the locomotor activation produced by psychostimulants and in the augmentation of this effect observed upon repeated drug administration (i.e. behavioral sensitization), although there is not a general consensus as to whether the nucleus accumbens-core or the nucleus accumbens-shell is preferentially involved in such alterations. This study was designed to evaluate the effects of acute amphetamine (0.20 mg/kg, s.c.) on dopamine output in the nucleus accumbens-shell and nucleus accumbens-core of the Roman lines under basal conditions (i.e. naïve rats) and after the repeated administration of amphetamine (1 mg/kg, s.c.؋10 days) or saline. We show that (1) in naïve rats, amphetamine caused a larger increment in dopamine output in the nucleus accumbens-shell vs the nucleus accumbens-core only in the Roman high-avoidance line; (2) repeated amphetamine elicits behavioral sensitization in Roman high-avoidance, but not Roman low-avoidance, rats; (3) in sensitized Roman highavoidance rats, amphetamine provokes a larger increment in dopamine output in the nucleus accumbens-core, and an attenuated dopaminergic response in the nucleus accumbens-shell, as compared with Roman high-avoidance rats repeatedly treated with saline; and (4) such neurochemical changes are not observed in the mesoaccumbens dopaminergic system of the sensitization-resistant Roman lowavoidance line. We propose that (1) Roman high-avoidance and Roman low-avoidance rats differ in the vulnerability to develop psychostimulant sensitization, (2) the nucleus accumbens-core and nucleus accumbens-shell subserve distinct functional roles in this phenomenon, and (3) comparative studies in the Roman lines may provide insight into the influence of neural substrates and genetic background on the individual vulnerability to addiction.
Brain Research, 1986
Microinjections of a monoclonal antibody against substance P (SP) into the nucleus accumbens (NAS) increased the concentrations of dopamine (DA) and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the NAS but not in neuroanatomically adjacent areas. SP immunoneutralization in the NAS also reduced the locomotor response to systemically administered D-amphetamine. Microinjections of control antibody did not significantly alter either DA metabolism or D-amphetamine-induced locomotion. These data are consistent with the hypothesis that endogenous SP modulates the release of DA in the NAS.