Extracellular dopamine in the rat ventral tegmental area and nucleus accumbens following ventral tegmental infusion of cocaine

Rats were implanted with dual dialysis probes, one in the ventral tegmental area, and another one ipsilateral in the nucleus accumbens. Infusion of cocaine (10, 100, 1000 mM) into the ventral tegmental area gradually increased extracellular dopamine to 164, 329 and 991% of baseline in the ventral tegmental area, but reduced dopamine to 76, 47 and 38% of baseline in the nucleus acumbens. These results are consistent with cocaine-induced feedback regulation of dopamine cell activity involving somatodendritec impulse-regulating dopamine D₂ autoreceptors.     

Blockade of D-1 dopamine receptors in the medial prefrontal cortex produces delayed effects on pre- and postsynaptic indices of dopamine function in the nucleus accumbens

The actions mediated by limbic system output projections of the basal ganglia were investigated by studying the effects of ventral pallidum (VP) stimulation on the activity of neurons in thalamic target nuclei, including several of the dorsal thalamic nuclei and the nucleus reticularis, using in vivo intracellular recordings in rats. Intracellular injection of Lucifer yellow was used in a subset of experiments to identify the neurons recorded and to confirm their location with respect to the specific thalamic nuclei targeted. Stimulation of the VP evoked ipsps in 79% of the mediodorsal cells recorded. In the reticular nucleus, 73% of the neurons tested responded with evoked ipsps. In contrast, in other dorsal thalamic nuclei VP stimulation evoked depolarizations in 58% of the cells recorded. The latency to onset of the ipsps in the mediodorsal nucleus and in the reticular nucleus were not substantially different (1.7 ± 1.1 msec vs. 2.7 ± 1.1 msec), whereas the depolarizing response evoked in dorsal thalamic nucleus neurons typically occurred at longer and more variable latencies (3.5 ± 2.7 msec).     

Suppression of attack behavior in cats by stimulation of ventral tegmental area and nucleus accumbens

Low frequency (6 pps) stimulation of ventral tegmental area (VTA) and nucleus accumbens (NA) produced EEG synchronization and suppressed attack behavior elicited by hypothalamic stimulation. Both quiet biting and affective attack with rage were suppressed. Autonomic and non-directed somatic motor components of the attack reaction were unaffected.High frequency (60 pps) stimulation of VTA failed to suppress any components of the attack reaction; high frequency stimulation of NA, however, did produce suppression of attack.Low frequency (6 pps) sensory stimulation, delivered by photic or lateral geniculate stimulation, produced EEG synchronization but failed to cause suppression of attack. These results indicate that low frequency stimulation per se does not cause suppression of ongoing behavior.This study demonstrates that VTA and NA, components of the mesolimbic dopamine system, are involved in the inhibition of emotional-type behaviors.     

Oxytocin injected into the ventral tegmental area induces penile erection and increases extracellular dopamine in the nucleus accumbens and paraventricular nucleus of the hypothalamus of male rats

The neuropeptide oxytocin (20-100 ng), induces penile erection when injected unilaterally into the caudal but not rostral mesencephalic ventral tegmental area (VTA) of male Sprague-Dawley rats. Such pro-erectile effect started 30 min after treatment and was abolished by the prior injection of d(CH2)5Tyr(Me)(2)-Orn(8)-vasotocin (1 microg), an oxytocin receptor antagonist injected into the same caudal ventral tegmental area or of haloperidol (1 microg), a dopamine receptor antagonist, injected either into the nucleus accumbens shell (NAs) or into the paraventricular nucleus of the hypothalamus (PVN) ipsilateral to the injected ventral tegmental area. Penile erection was seen 15 min after the occurrence of, or concomitantly to, an increase in extracellular dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the dialysate obtained from the nucleus accumbens or the paraventricular nucleus, which was also abolished by d(CH2)5Tyr(Me)(2)-Orn(8)-vasotocin (1 microg), injected into the ventral tegmental area before oxytocin. In the caudal ventral tegmental area oxytocin-containing axons/fibres (originating from the paraventricular nucleus) appeared to closely contact cell bodies of mesolimbic dopaminergic neurons retrogradely labelled with Fluorogold injected into the nucleus accumbens shell, suggesting that oxytocin effects are mediated by the activation of mesolimbic dopaminergic neurons, followed in turn by that of incerto-hypothalamic dopaminergic neurons impinging on oxytocinergic neurons mediating penile erection. As the stimulation of paraventricular dopamine receptors not only induces penile erection, but also increases mesolimbic dopamine neurotransmission by activating oxytocinergic neurons, these results provide further support for the existence of a neural circuit in which dopamine and oxytocin influence both the consummatory and motivational/rewarding aspects of sexual behaviour.     

Laterodorsal tegmental stimulation elicits dopamine efflux in the rat nucleus accumbens by activation of acetylcholine and glutamate receptors in the ventral tegmental area

Cholinergic and glutamatergic neurons in the laterodorsal tegmentum (LDT) and neighbouring mesopontine nuclei are thought to influence mesolimbic dopaminergic neuronal activity involved in goal-directed behaviours. We measured the changes in dopamine oxidation current (corresponding with dopamine efflux) in the nucleus accumbens (NAc) in response to electrical stimulation of the LDT using in vivo chronoamperometry in urethane-anaesthetized rats. LDT stimulation (35 Hz pulse trains for 60 s, 1 s intertrain interval) evoked a three-component change in dopamine efflux in the NAc: (i) an initial stimulation time-locked increase in the dopamine signal above baseline, followed by (ii) an immediate decrease below baseline, and thereafter by (iii) a prolonged increase in the dopamine signal above baseline. Intra-VTA infusion of the nicotinic receptor antagonist mecamylamine (5 microg/0.5 microL) or the ionotropic glutamate receptor antagonist kynurenate (10 microg/microL) attenuated the first LDT-elicited component. The second suppressive component was abolished by intra-LDT infusions of either the nonselective or the M2-selective muscarinic receptor antagonists scopolamine (100 microg/microL) and methoctramine (50 microg/microL), respectively. In contrast, intra-VTA infusions of scopolamine (200 microg/microL) resulted in a selective attenuation of the third facilitatory component, whereas both second and third components were abolished by systemic injections of scopolamine (5 mg/kg). These results suggest that the initial increase, subsequent decrease, and final prolonged increase in extracellular dopamine levels in the NAc are selectively mediated by LDT-elicited activation of (i) nicotinic and glutamatergic receptors in the VTA, (ii) muscarinic M2 autoreceptors on LDT cell bodies, and (iii) muscarinic receptors in the VTA, respectively.     

Comparison of G-protein activation in the brain by μ-, δ-, and κ-opioid receptor agonists in μ-opioid receptor knockout mice

Mice lacking the μ-opioid receptor gene have been developed by a gene knockout procedure. In this study, the activity of opioid receptor coupled G-proteins was examined to investigate whether there is a change in the extent of coupling for μ-, δ-, and κ-opioid receptors in μ-opioid receptor knockout mice. Selective agonists of μ- (DAMGO), δ- (DPDPE), and κ- (U-69,593) opioid receptors stimulated [³⁵S]GTPγS binding in the caudate putamen and cortex of wild-type mice. In contrast, only U-69,593 stimulated [³⁵S]GTPγS binding in these regions of μ-opioid receptor knockout mice. These results confirmed the absence of G-protein activation by a μ-opioid receptor agonist in μ-opioid receptor knockout mice, and demonstrated that coupling of the κ-opioid receptor to G-proteins is preserved in these mice. However, G-protein activation by the δ-opioid receptor agonist, DPDPE, was reduced in the μ-opioid receptor knockout mice, at least in the brain regions studied using autoradiography.     

Effects of corticotropin-releasing hormone receptor antagonists on cocaine-induced dopamine overflow in the medial prefrontal cortex and nucleus accumbens of rats

Recent evidence suggests an important role for corticotropin-releasing hormone (CRH) and CRH receptors in cocaine reinforcement. CRH receptor antagonists reduce cocaine self-administration and attenuate the reinstatement of extinguished cocaine-seeking behavior, but little is known about the mechanisms involved. One possible mechanism for these effects may involve the cocaine-induced activation of CRH located in brain regions outside of the hypothalamus. CRH has been shown to increase dopaminergic transmission in regions relevant for cocaine reinforcement, such as the medial prefrontal cortex and the nucleus accumbens. Here, we report that CP-154,526, a CRH1-receptor antagonist, actually enhances cocaine-induced increases in dopamine overflow in the medial prefrontal cortex, measured using in vivo microdialysis. In contrast, the receptor antagonist did not alter cocaine-induced increases in dopamine in most of the nucleus accumbens, except for the most rostral part. These data suggest a surprising role for prefrontal cortex dopamine in the ability of CRH-receptor antagonists to attenuate cocaine seeking in rats.     

Reduction of dopamine utilization in the prefrontal cortex but not in the nucleus accumbens after selective destruction of noradrenergic fibers innervating the ventral tegmental area in the rat

The present study was made to determine the role of the noradrenergic (NA) neurons which innervate the ventral tegmental area (VTA) in the regulation of VTA dopaminergic (DA) neurons projecting to the prefrontal cortex and the nucleus accumbens. For this purpose, a 6-hydroxydopamine lesion was made in benzotropine pretreated rats medially just above the decussatio of the pedunculus cerebellaris superior in order to specifically destroy the NA fibers innervating the VTA without affecting those projecting to the prefrontal cortex. Seven days later the ratio of DOPAC and DA levels was estimated in the prefrontal cortex and the nucleus accumbens and used as an index of DA utilization. In the lesioned rats the DOPAC/DA ratio was significantly decreased in the prefrontal cortex but not in the nucleus accumbens. These results suggest that the NA neurons which innervate the VTA exert a specific tonic excitatory influence on the mesocortico-prefrontal DA neurons.     

Chronic nicotine and smoke treatment modulate dopaminergic activities in ventral tegmental area and nucleus accumbens and the gamma-aminobutyric acid type B receptor expression of the rat prefrontal cortex

Dopaminergic afferents from the mesencephalic areas, such as ventral tegmental area (VTA), synapse with the gamma-aminobutyric acid (GABA)-ergic interneurons in the prefrontal cortex (PFC). Pharmacological and electrophysiological data show that the reinforcement, the dependence-producing properties, as well as the psychopharmacologic effects of nicotine depend to a great extent on activation of nicotinic receptors within the mesolimbocortical dopaminergic projection. To explore further the relationship between the mesencephalic dopaminergic neurons and PFC GABAergic neurons, we investigated the effects of nicotine and passive exposure to cigarette smoke on the regulation of tyrosine hydroxylase (TH) in VTA and substantia nigra (SNC) and dopamine (DA) D1 receptor levels in nucleus accumbens (NAc) and caudate-putamen (CPu). Also, the simultaneous changes in GABAB receptors mRNAs in the PFC were studied. The results showed that chronic nicotine and smoking treatment differentially changed the levels of TH protein in VTA and SNC and DA D1 receptor levels in Nac and CPu. GABAB1 and GABAB2 receptor mRNA levels also showed different change patterns. Ten and thirty minutes of smoke exposure increased GABAB1 receptor mRNA to a greater extent than that of GABAB2, whereas GABAB2 was greatly enhanced after 1 hr of smoke exposure. The TH levels in VTA were closely related to DA D1 receptor levels in NAc and with GABAB receptor mRNA changes in PFC. These results suggest that the mesolimbic pathway and GABAB receptor mRNA in PFC are modulated by nicotine and cigarette smoke, implying an important role in nicotine's psychopharmacological effects.     

Facilitatory modulation of mesolimbic dopamine neuronal activity by a μ-opioid agonist and nicotine as examined with in vivo microdialysis

Administration of either Tyr-d-Ala-Gly-MePhe-Gly(ol) (DAGO), a μ-opioid agonist, or nicotine into the VTA (A10) caused an increase in both dopamine (DA) and its metabolite levels in both the A10 region and DA nerve terminals in the nucleus accumbens of rats when assessed with dual probe brain dialysis. These findings show that DAGO and nicotine increase both axonal- and somatodendritic-DA release, as well as metabolic activity in mesolimbic DA neurons, possibly by inducing an increase in neuronal impulse flow.     

Excitatory amino acid receptor subtype agonists induce feeding in the nucleus accumbens shell in rats: opioid antagonist actions and interactions with μ-opioid agonists

Administration of μ-opioid receptor subtype agonists into the nucleus accumbens shell elicits feeding which is dependent upon the normal function of μ-, δ- and κ-opioid receptors, D₁ dopamine receptors and GABA_B receptors in the nucleus accumbens shell for its full expression. Whereas the AMPA antagonist, DNQX administered into the nucleus accumbens shell elicits a transient, though intense feeding response, feeding is elicited by excitatory amino acid agonists administered into the lateral hypothalamus. The present study examined whether excitatory amino acid agonists elicited feeding following administration into the nucleus accumbens shell of rats, whether such feeding responses were altered by opioid antagonist pretreatment, and whether such feeding responses interacted with feeding elicited by μ-opioid agonists. Both AMPA (0.25–0.5 μg) and NMDA (1 μg) in the nucleus accumbens shell significantly and dose-dependently increased food intake over 4 h. Both feeding responses were blocked by naltrexone pretreatment in the nucleus accumbens shell. The μ-opioid agonist, [D-Ala²,NMe-Phe⁴,Gly-ol⁵]-enkephalin in the nucleus accumbens shell significantly increased food intake which was significantly enhanced by AMPA cotreatment. This enhanced feeding response was in turn blocked by pretreatment with either general or μ-selective opioid antagonists. In contrast, cotreatment of NMDA and the μ-opioid agonist in the nucleus accumbens shell elicited feeding which was significantly less than that elicited by either treatment alone. These data indicate the presence of important interactions between excitatory amino acid receptors and μ-opioid receptors in the nucleus accumbens shell in mediating feeding responses in nondeprived, ad libitum-fed rats.     

Up-regulation of spinal μ-opioid receptor function to activate G-protein by chronic naloxone treatment

The effects of repeated s.c. administrations of an μ-opioid receptor antagonist naloxone on the G-protein activation induced by μ-opioid receptor agonists [ -Ala²,N-MePhe⁴,Gly-ol⁵]enkephalin (DAMGO), endomorphin-1 and endomorphin-2 in the mouse spinal cord was studied, monitoring guanosine-5′-o-(3-[³⁵S]thio)triphosphate ([³⁵S]GTPγS) binding. All μ-opioid receptor agonists concentration-dependently increased the [³⁵S]GTPγS binding. The increases of [³⁵S]GTPγS binding induced by agonists were significantly enhanced in mice pretreated with naloxone. Under the present condition, chronic treatment with naloxone significantly increased the density of [³H]DAMGO binding sites with an increase in K_d values in spinal cord membranes, indicating an increase in μ-opioid receptors on the membrane surface. These findings suggest that chronic treatment with an μ-opioid receptor antagonist naloxone leads to the supersensitivity to activate G-protein by μ-opioid receptor agonists with an increase in μ-opioid receptors in membranes of the mouse spinal cord.     

Enhanced apomorphine sensitivity and increased binding of dopamine D2 receptors in nucleus accumbens in prepubertal rats after neonatal blockade of the dopamine D3 receptors by (+)-S14297

The role of dopamine (DA) D3 receptors is controversial in early developmental stages of specially locomotor activity. Past studies have only tested behavioral changes induced by neonatal administration of nonselective dopamine antagonist such as haloperidol or sulpiride in adult rats. We investigated the role of neonatal blockade of DA D3 receptors at (postnatal day, P1 to P12) using the DA D3 receptor antagonist (+)-S14297 on paradigms related to DA behaviors including locomotor activity in novel environment and after administration of the DA nonspecific agonists d-amphetamine, and apomorphine. Additionally, autoradiographic studies were performed to correlate behavioral alterations with DA D1-like, D2-like, and D3 receptors. All studies were performed at two critical ages, prepubertal (P35) and postpubertal (P60). The quantitative autoradiogaphic study revealed increases in the expression of DA D2-like receptor expression in the nucleus accumbens (NAcc) in prepubertal animals that received the DA D3 antagonist (+)-S14297 at neonatal age. In addition, novel environment and apomorphine administration (0.5 mg/kg, s.c.), induced increases of locomotor activity in prepubertal animals that received the DA D3 antagonist (+)-S14297. Autoradiographic and behavioral results suggest that blockade of DA D3 receptors after birth may mediate different neurodevelopmental aspects of the dopaminergic pathway before and after puberty.     

Site-specific activation of dopamine and serotonin transmission by aniracetam in the mesocorticolimbic pathway of rats

The effects of aniracetam on extracellular levels of dopamine (DA), serotonin (5-HT) and their metabolites were examined in five brain regions in freely moving stroke-prone spontaneously hypertensive rats (SHRSP) using in vivo microdialysis. Basal DA release in SHRSP was uniformly lower in all regions tested than that in age-matched control Wistar Kyoto rats. 3,4-Dihydroxyphenylacetic acid and homovanillic acid levels were altered in the basolateral amygdala, dorsal hippocampus and prefrontal cortex of SHRSP. While basal 5-HT release decreased in the striatum and increased in the basolateral amygdala, there was no associated change in 5-hydroxyindoleacetic acid levels. Systemic administration of aniracetam to SHRSP enhanced both DA and 5-HT release with partly associated change in their metabolite levels in the prefrontal cortex, basolateral amygdala and dorsal hippocampus, but not in the striatum and nucleus accumbens shell, in a dose-dependent manner (30 and/or 100 mg/kg p.o.). Microinjection (1 and 10 ng) of aniracetam or its metabolites (N-anisoyl-GABA and 2-pyrrolidinone) into the nucleus accumbens shell produced no turning behavior. These findings indicate that SHRSP have a dopaminergic hypofunction throughout the brain and that aniracetam elicits a site-specific activation in mesocorticolimbic dopaminergic and serotonergic pathways in SHRSP, possibly via nicotinic acetylcholine receptors in the ventral tegmental area and raphe nuclei. The physiological roles in the aniracetam-sensitive brain regions may closely link with their clinical efficacy towards emotional disturbances appearing after cerebral infarction.     

Attenuated extracellular dopamine levels after stress and amphetamine in the nucleus accumbens of rats with neonatal ventral hippocampal damage

Summary. In vivo microdialysis was used to study the effects of restraint stress (30 min) and amphetamine (AMPH) (5 mg/kg, i.p.) in awake adult male rats with neonatal ventral hippocampal (VH) damage. Extracellular levels of dopamine (DA), dihydrophenylacetate (DOPAC), homovanillate (HVA) and 5-hydroxyindolacetate (5-HIAA) were measured in the nucleus accumbens (NA). There were no differences in the baseline levels of DA, DOPAC, HVA or 5-HIAA in the lesioned as compared to the sham rats. Release from restraint resulted in increased extracellular levels of DA in the sham but not in the lesioned animals. AMPH increased DA release in both sham operated and lesioned animals, but this increase was significantly attenuated in the lesioned rats. Our data suggest that this developmental lesion alters function of the dopaminergic system in response to environmental and pharmacological challenge. Received June 3, 1997; accepted August 10, 1998     

伏隔核毁损对MAP模型大鼠行为及脑内DA受体的影响

目的 探讨立体定向伏隔核毁损对甲基苯丙胺（MAP）模型大鼠行为学及不同脑区多巴胺D2受体表达的影响。方法 将80只SD大鼠随机分为对照组、模型组、假手术组和手术组，每组各20只。经腹腔注射MAP制备精神分裂症模型，采用立体定向一直流电毁损伏隔核，观察大鼠刻板行为变化；并采用原位杂交法观察额叶、颞叶、边缘区及脑干部位的D2受体表达。结果 与对照组比较，模型组及假手术组大鼠刻板行为评分及各个脑区D2受体表达均显著性增加；与模型组及假手术组比较，手术组大鼠刻板行为评分及各脑区DA受体阳性细胞数目均显著性减少。结论 伏隔核毁损可能通过抑制MAP诱发的脑内D2表达亢进而改变其行为学异常。     

Dopamine efflux in the rat nucleus accumbens evoked by dopamine receptor stimulation in the entorhinal cortex is modulated by oestradiol and progesterone

This study compared the effects of dopamine receptor stimulation in the entorhinal cortex on dopamine release in the nucleus accumbens, measured by in vivo microdialysis in conscious Sprague-Dawley rats, with and without oestradiol and progesterone priming. Nonselective dopamine receptor stimulation with apomorphine reduced dopamine release in the nucleus accumbens, an effect which was prevented by injection of cis-flupenthixol into the entorhinal cortex. Selective D₁ receptor stimulation with SKF38393 increased dopamine release, whereas selective D₂ receptor stimulation with quinpirole did not affect dopamine release. Combined administration of oestradiol and progesterone potentiated the response to apomorphine and prevented the response to SKF38393. The effects of single hormone administration on the response to apomorphine suggested that the modulation was primarily due to oestradiol enhancing effects of progesterone. Experiments with high [K⁺] suggested these hormonal effects were exerted predominantly in the entorhinal cortex. The present experiments have demonstrated that dopaminergic modulation of transmission in a cortico-striatal loop linking temporal and prefrontal cortex is regulated by oestradiol and progesterone. Dysfunction in this system in humans may give rise to affective and cognitive symptoms which may, if initiated by a postpartum fall in oestrogen and progesterone concentrations, constitute the core pathophysiology of puerperal psychosis. Synapse 25:37–43, 1997. © 1997 Wiley-Liss, Inc.     

Stress-induced analgesia in μ-opioid receptor knockout mice reveals normal function of the δ-opioid receptor system

Stress-induced analgesia (SIA) was examined in wildtype and μ-opioid receptor knockout mice. We used thermal paw withdrawal (TPW) latency following a continuous 3-min swim in 20°C water, and found a significant increase in TPW latency in both wild-type and knockout mice. Pre-treatment prior to the swim with naltrindole, a selective δ-opioid receptor antagonist, blocked the increase in TPW latency in knockout mice. These results demonstrate an intact δ-receptor-mediated function of a physiologically-released endogenous agonist in the μ-opioid receptor knockout mouse. The present findings are in contrast with previous reports that analgesia induced by exogenous delta agonists is reduced in the knockout mice.     

Non-NMDA excitatory amino acid receptors in the ventral tegmental area mediate systemic dizocilpine (MK-801) induced hyperlocomotion and dopamine release in the nucleus accumbens

This study investigated the putative role of non-NMDA excitatory amino acid (EAA) receptors in the ventral tegmental area (VTA) for the increase in dopamine (DA) release in the nucleus accumbens (NAC) and behavioral stimulation induced by systemically administered dizocilpine (MK-801). Microdialysis was utilized in freely moving rats implanted with probes in the VTA and NAC. Dialysates from the NAC were analyzed with high-performance liquid chromatography for DA and its metabolites. The VTA was perfused with the AMPA and kainate receptor antagonist CNQX (0.3 or 1 mM) or vehicle. Forty min after onset of CNQX or vehicle perfusion of the VTA, MK-801 (0.1 mg/kg) was injected subcutaneously. Subsequently, typical MK-801 induced behaviors were also assessed in the same animals by direct observation. MK-801 induced hyperlocomotion was associated with a 50% increase of DA levels in NAC dialysates. Both the MK-801 evoked hyperlocomotion and DA release in the NAC was antagonized by CNQX perfusion of the VTA in a concentration-dependent manner. None of the other rated MK-801 evoked behaviors, e.g. head weaving or sniffing, were affected by CNQX perfusion of the VTA. By itself the CNQX or vehicle perfusion of the VTA alone did not affect DA levels in NAC or any of the rated behaviors. These results indicate that MK-801 induced hyperlocomotion and DA release in the NAC are largely elicited within the VTA via activation of non-NMDA EAA receptors, tentatively caused by increased EAA release. Thus, the locomotor stimulation induced by psychotomimetic NMDA receptor antagonists may not only reflect impaired NMDA receptor function, but also enhanced AMPA and/or kainate receptor activation in brain, e.g., in the VTA. In view of their capacity to largely antagonize the behavioral stimulation induced by psychotomimetic drugs, such as MK-801, AMPA, and/or kainate receptor antagonists may possess antipsychotic efficacy. J. Neurosci. Res. 51:583–592, 1998. © 1998 Wiley-Liss, Inc.     

In vivo neurochemical evidence that stimulation of accumbal GABAA and GABAB receptors each reduce acetylcholine efflux without affecting dopamine efflux in the nucleus accumbens of freely moving rats

Cholinergic neurons in the nucleus accumbens contain GABA_A and GABA_B receptors that are thought to inhibit neural activity. We analyzed the roles of GABA_A and GABA_B receptors in regulating accumbal acetylcholine efflux of freely moving rats using in vivo microdialysis. The effects of GABA receptor ligands on the accumbal dopamine efflux were also analyzed because accumbal cholinergic and dopaminergic neurons could mutually interact. Drugs were applied intracerebrally through the dialysis probe. Doses of compounds indicate total amount administered (mol) during 30–60 min infusions. To monitor basal acetylcholine, a low concentration of physostigmine (50 nM) was added to the perfusate. GABA_A receptor agonist muscimol (3 and 30 pmol) induced a dose‐related decrease in accumbal acetylcholine. GABA_B receptor agonist baclofen (30 and 300 pmol) also produced a dose‐related decrease in acetylcholine. GABA_A receptor antagonist bicuculline (60 pmol) which failed to alter baseline acetylcholine counteracted the muscimol (30 pmol)‐induced decrease in acetylcholine. GABA_B receptor antagonist 2‐hydroxysaclofen (12 nmol) which failed to change baseline acetylcholine, counteracted the baclofen (300 pmol)‐induced decrease in acetylcholine. Neither muscimol (30 pmol) nor baclofen (300 pmol) which reduced accumbal acetylcholine altered baseline accumbal dopamine. Neither bicuculline (60 pmol) nor 2‐hydroxysaclofen (12 nmol) also affected the baseline dopamine. These results show that GABA_A and GABA_B receptors each exert inhibitory roles in the regulation of accumbal cholinergic neural activity. The present results also provides in vivo neurochemical evidence that stimulation of GABA_A and GABA_B receptors each reduce acetylcholine efflux without affecting dopamine efflux in the nucleus accumbens of freely moving rats.