甲基苯丙胺急性处理对大鼠纹状体中神经元和谷氨酸转运体的影响

目的:观察甲基苯丙胺(METH)急性处理致神经损伤情况,以及纹状体中谷氨酸转运体1(GLT1)与囊泡型谷氨酸转运体1(VGLUT1)的变化。方法:建立METH急性毒性模型,同时利用谷氨酸转运体激动剂头孢曲松调控谷氨酸转运体的表达,尼氏染色实验观测神经元中尼氏小体的变化,利用Western blot实验检测其谷氨酸转运体蛋白表达的变化。结果:与盐水对照组相比,METH给药组刻板行为明显增加(P<0.01),尼氏小体显著减少,纹状体中GLT1和VGLUT1的表达增加分别为23.1%和66.1%(P<0.05);与METH组相比,头孢曲松预防给药组大鼠刻板行为明显减少,纹状体中GLT1的表达增加15.2%(P<0.05),VGLUT1的表达降低,但没有统计学意义(P>0.05)。结论:METH急性处理能导致神经损伤,引起纹状体中谷氨酸转运体的表达变化;头孢曲松能激活谷氨酸转运体的表达,缓解METH引起的神经损伤。     

头孢曲松对甲基苯丙胺致大鼠行为及纹状体氨基酸等递质含量改变的影响

目的观察甲基苯丙胺(METH)急性处理时致神经损伤情况,以及纹状体中氨基酸类神经递质谷氨酸(glutamate,Glu)、单胺类神经递质多巴胺(dopamine,DA)及其代谢产物DOPAC的变化。方法建立METH急性毒性模型,同时利用药物头孢曲松进行干预,利用清醒动物脑微透析技术检测神经递质含量的变化。结果 METH急性给药组与盐水对照组相比,刻板行为明显增加(P<0.01);急性给予METH后,胞外Glu浓度持续增加,在本试验检测时间(0～6 h)范围内,与基础平衡值相比,在给药5.5 h时Glu浓度已增加450%。胞外DA水平在1 h达峰值,与基础平衡值相比,浓度增加1248.6%。与METH组相比,头孢曲松预防给药可明显降低大鼠纹状体胞外Glu浓度(P<0.05)。结论 METH急性处理能引起纹状体中胞外谷氨酸的含量明显增加,导致神经损伤;METH的神经毒性与兴奋性氨基酸的过度释放密切相关。     

乙醇促进大鼠纹状体隔核抗坏血酸的释放

应用脑内微透析技术结合ＨＰＬＣ－ＥＣＤ法检测显示，乙醇（２．５，５．０ｇ·ｋｇ－１，ｉｐ）显著增加大鼠纹状体和伏隔核抗坏血酸的释放。５．０ｇ·ｋｇ－１乙醇可使纹状体和伏隔核释放峰值达３０％以上，对伏隔核抗坏血酸的影响持续时间长于纹状体。提示脑中抗坏血酸参与乙醇对中枢神经系统的作用。     

伏隔核黑色素聚集激素在大鼠甲基苯丙胺行为敏化中的作用

目的黑色素聚集激素(Melanin-Concentrating Hor-mone,MCH)是由19个氨基酸组成的环形神经肽,研究发现伏隔核的MCH及其受体能够间接调节细胞外调节激酶(ERK)的活性,参与中枢神经系统突触可塑性的调节。本研究的目的在于探索伏隔核MCH在大鼠甲基苯丙胺诱导的行为敏化中的作用。方法①于外侧伏隔核(NAc shell)或中央伏隔核(NAc core)微注射MCH,考察其对于大鼠甲基苯丙胺诱导的行为敏化形成的作用。每日给予大鼠甲基苯丙胺注射,注射前30 min给予MCH(隔日微注射一次),后立即测定2h自发活动,连续14 d。②NAc shell或NAc core微注射MCH,考察其对甲基苯丙胺诱导的行为敏化表达的影响。每日给予大鼠甲基苯丙胺注射并进行2 h自发活动的测定,连续14 d。戒断7 d后进行甲基苯丙胺challenge,注射前30min于NAc shell或NAc core微注射MCH,后立即测定2 h自发活动。③于NAc shell或NAc core微注射MCH受体特异性拮抗剂SNAP94847,考察其对大鼠甲基苯丙胺诱导的行为敏化的作用,方法同1。④NAc shell或NAc core微注射SNAP94847,考察SNAP94847对于甲基苯丙胺诱导的行为敏化表达的影响,方法同2。结果 NAc shell微注射MCH能够抑制大鼠甲基苯丙胺诱导的行为敏化的形成,而NAc core没有此作用;NAc shell或core微注射MCH对甲基苯丙胺诱导的行为敏化表达都没有影响。NAc shell微注射SNAP94847能够易化行为敏化的形成,而NAc core没有此作用;NAc shell或core微注射SNAP94847对行为敏化表达都没有影响。结论 NAc shell处的MCH及其受体可能参与了大鼠甲基苯丙胺诱导的行为敏化的形成过程。     

甲基苯丙胺对大鼠行为和脑组织多巴胺及其代谢产物含量的影响

甲基苯丙胺（methamphetamine，MA）属于苯丙胺类兴奋剂，其盐酸盐为无色透明的晶体，状如冰，俗称“冰毒”。MA最初是作为减肥药、抗疲劳剂使用，随后发现其具有精神依赖性。上世纪50年代，欧美国家出现MA滥用。近年国际上的滥用呈上升趋势，国内大中城市的滥用情况也十分严峻。MA除对心、肝、肺、肾和骨骼肌等有毒性作用外，还有较强的神经毒性。     

吗啡依赖对大鼠伏隔核神经甾体和氨基酸递质的影响

目的　利用大鼠吗啡依赖模型,观察吗啡依赖及戒断对大鼠伏隔核中神经甾体和氨基酸类神经递质水平影响。方法　腹腔注射递增剂量的盐酸吗啡使雄性SD大鼠形成吗啡依赖,并用纳洛酮催促戒断。分离吗啡依赖和戒断大鼠的伏隔核。经液液萃取和固相萃取法提取脱氢表雄酮、孕烯醇酮、别孕烯醇酮、脱氢表雄酮硫酸酯和孕烯醇酮硫酸酯,并采用高效液相色谱质谱系统检测其含量。采用柱前衍生-电化学检测-高效液相色谱法测定甘氨酸、谷氨酸和γ氨基丁酸的含量。结果　与对照组相比,纳洛酮催促戒断时,吗啡依赖大鼠伏隔核脱氢表雄酮硫酸酯的水平下降(P<0 .05),孕烯醇酮(P<0 .01 )和谷氨酸(P<0 .05 )水平均升高。结论　吗啡戒断时大鼠伏隔核的谷氨酸系统处于兴奋状态,伏隔核中的内源性神经甾体在吗啡依赖和戒断的形成中发挥作用。     

毁损伏隔核对恒河猴吗啡觅药行为的影响

目的:了解灵长类动物伏隔核在药物强化效应中的作用。方法:通过吗啡强化形成条件性位置偏爱,毁损实验猴伏隔核,利用条件性位置偏爱实验测定术前、术后吗啡依赖猴对注射吗啡侧的偏好分,评价猴伏隔核在药物强化效应中的作用。结果:依赖实验组猴术前在黑箱停留的时间为793 .6s±s 2 6 .4s,术后为5 12 .7s±s 2 0 .3s ,依赖对照组术后在黑箱停留时间为786 .5s±s 2 2 .8s,毁损猴双侧伏隔核能够完全消除位置偏爱行为。结论:猴伏隔核在药物强化作用中起着重要作用。     

吗啡急性给药对大鼠伏隔核中神经甾体水平的影响

目的:观察吗啡急性给药后大鼠伏隔核中神经甾体水平的变化.方法:给3组大鼠腹腔分别注射0.5、5和20 mg/kg的盐酸吗啡,分别于给药后0.5和2 h将大鼠断头处死,分离伏隔核.经液-液萃取和固相萃取法提取脱氢表雄酮、孕烯醇酮和别孕烯醇酮,并采用高效液相色谱-质谱系统检测其含量.结果:与对照组比较,0.5 mg/kg剂量的吗啡使大鼠伏隔核中脱氢表雄酮水平显著降低,而5 mg/kg剂量的吗啡则使脱氢表雄酮水平显著升高;20 mg/kg剂量的吗啡使大鼠血浆中的别孕烯醇酮水平显著升高.结论:大鼠伏隔核中的脱氢表雄酮可能在吗啡急性给药的效应中发挥重要作用.     

吗啡急性给药对大鼠伏隔核中神经甾体水平的影响

目的:观察吗啡急性给药后大鼠伏隔核中神经甾体水平的变化.方法:给3组大鼠腹腔分别注射0.5、5和20 mg/kg的盐酸吗啡,分别于给药后0.5和2 h将大鼠断头处死,分离伏隔核.经液-液萃取和固相萃取法提取脱氢表雄酮、孕烯醇酮和别孕烯醇酮,并采用高效液相色谱-质谱系统检测其含量.结果:与对照组比较,0.5 mg/kg剂量的吗啡使大鼠伏隔核中脱氢表雄酮水平显著降低,而5 mg/kg剂量的吗啡则使脱氢表雄酮水平显著升高;20 mg/kg剂量的吗啡使大鼠血浆中的别孕烯醇酮水平显著升高.结论:大鼠伏隔核中的脱氢表雄酮可能在吗啡急性给药的效应中发挥重要作用.     

海洛因诱导条件性位置偏爱大鼠伏隔核的转录组学研究

目的 研究海洛因依赖对大鼠伏隔核的转录组和代谢组的影响。方法 将8只SD大鼠随机分成生理盐水对照组和海洛因诱导组,两组大鼠均采用剂量递增法分别经皮下注射生理盐水和海洛因,连续注射7 d,建立海洛因诱导位置偏爱模型。实验第8天将2组大鼠断头取脑,剥离伏隔核,提取RNA进行转录组学检测,分析海洛因依赖大鼠伏隔核相关基因的差异性表达。结果 与对照组比较,根据DESeq2 P值<0.05 |log2样本间表达量比值|>0筛选标准,海洛因依赖大鼠的测序数据共926个差异基因,其中上调基因410个,下调基因516个。GO功能富集中,生物过程(BP)分析,与对照组相比,Heroin组在突触可塑性的调节、谷氨酸受体信号通路的调节、长时程突触增强效力等方面上调,在固醇、酒精及有机羟基化合物等的代谢及生物合成过程方面下调。细胞组成(CC)方面提示谷胱甘肽突触基因表达升高,核糖体、内线粒体膜蛋白复合物等基因表达下降。分子功能(MF)中,糖皮质激素受体结合基本生化活性中的基因表达升高,核糖体的结构成分等基因降低。KEGG通路富集中海洛因组在MAPK信号通路、黑色素生成和胆碱能突触等方面上调;在类固...     

伏隔核胆碱能神经元在线索诱导的海洛因复吸中的作用

目的 比较不同的二醋吗啡(海洛因)戒断时间对于环境线索(CC)或条件性线索(CS)诱导的大鼠复吸行为的影响,并探讨伏隔核胆碱能神经元可能的调节作用。方法 SD大鼠进行海洛因自身给药训练,每天4 h, 连续14 d,建立海洛因自身给药模型。随后置饲养笼自然戒断,随机分为第1天CC(d 1CC)组、d 14 CC组、d 1 CC+CS组和d 14 CC+CS组。测定有效鼻触次数,免疫组化双标法检测伏隔核(NAc)壳部和NAc核部胆碱乙酰转移酶(ChAT)与c-Fos共表达的水平。结果 海洛因自身给药大鼠随着戒断时间延长,CC诱导的海洛因觅药行为的恢复,即d 14 CC组与d 1 CC组比较,有效鼻触数明显增加(P<0.05);海洛因自身给药大鼠相同时间戒断后,不同线索诱导的海洛因觅药行为的恢复,即d 1 CC+CS组与d 1 CC组比较,以及d 14 CC+CS组与d 14 CC组比较,有效鼻触数均明显增加(P<0.05)。同时,在NAc壳部,与d 1 CC组比较,d 14 CC组大鼠的ChAT, c-Fos, ChAT+c-Fos免疫阳性细胞数分别为114±9,15±6,(13±5)个,ChAT+c-Fos占ChAT百分比为(11±4)%,明显增加(P<0.05);在NAc壳部和NAc核部,与d 1 CC组比较,d 1 CC+CS组大鼠的上述表达没有差异;在NAc壳部和NAc核部,与d 14 CC组比较,d 14 CC+CS组的ChAT, ChAT+c-Fos免疫阳性细胞数均明显减少(P<0.05)。结论 随着戒断时间的延长,CC诱导的海洛因觅药行为的增加,可能与NAc壳部胆碱能神经元的激活增多有关;而CS诱导的海洛因觅药行为的增加,可能与NAc壳部和核部胆碱能神经元的激活减少有关。     

Control of within-binge cocaine-seeking by dopamine and glutamate in the core of nucleus accumbens

Rationale  Dopamine and glutamate are thought to interact in the ventral striatum and to play important roles there in the cocaine-seeking of cocaine-experienced animals. Objectives  We sought to determine the relative roles of the two transmitters in the two major zones of the nucleus accumbens (NAS), the core and shell subregions. Methods  We assessed the effects of dopamine and glutamate receptor blockade in the core and shell on intravenous cocaine self-administration in rats. Trained animals were allowed to self-administer cocaine for an initial hour, and then D1-type or D2-type dopamine receptor blockers or NMDA-type or AMPA-type glutamate receptor blockers were infused by reverse microdialysis into one of the two regions for an additional 3 h of testing. Results  The D1-type antagonist SCH23390 and the D2-type antagonist raclopride each increased cocaine intake whereas the AMPA-type antagonist CNQX decreased responding when infused into the core. SCH23390 increased cocaine intake less strongly when infused into the shell, while raclopride and CNQX were each ineffective when infused into the shell. The NMDA-antagonist CPP failed to affect cocaine self-administration when infused into either site. Conclusions  These findings implicate the core of NAS in the maintenance of established cocaine self-administration in trained animals, despite the fact that the reinforcement of responding in untrained animals appears to results from cocaine actions in the olfactory tubercle and medial shell and not the core of accumbens.     

Blockade of mGluR5 in the nucleus accumbens shell but not core attenuates heroin seeking behavior in rats

Aim:

Glutamatergic neurotransmission in the nucleus accumbens (NAc) is crucial for the relapse to heroin seeking. The aim of this study was to determine whether mGluR5 in the NAc core or shell involved in heroin seeking behavior in rats.

Methods:

Male SD rats were self-administered heroin under a fixed-ratio 1 (FR1) reinforcement schedule for 14 d, and subsequently withdrawn for 2 weeks. The selective mGluR5 antagonist 2-methyl-6-phenylethynyl-pyridine (MPEP, 5, 15 and 50 nmol per side) was then microinjected into the NAc core or shell 10 min before a heroin-seeking test induced by context, cues or heroin priming.

Results:

Microinjection of MPEP into the NAc shell dose-dependently decreased the heroin seeking induced by context, cues or heroin priming. In contrast, microinjection of MPEP into the NAc core did not alter the heroin seeking induced by cues or heroin priming. In addition, microinjection with MPEP (15 nmol per side) in the NAc shell reversed both the percentage of open arms entries (OE%) and the percentage of time spent in open arms (OT%) after heroin withdrawal. Microinjection of MPEP (50 nmol per side) in the striatum as a control location did not affect the heroin seeking behavior. Microinjection of MPEP in the 3 locations did not change the locomotion activities.

Conclusion:

Blockade of mGluR5 in NAc shell in rats specifically suppresses the relapse to heroin-seeking and anxiety-like behavior, suggesting that mGluR5 antagonists may be a potential candidate for the therapy of heroin addiction.     

Effects of serotonergic activity in nucleus accumbens septi on drug-induced circling

The effects of injections of 5-hydroxytryptamine (5-HT) into the nucleus accumbens and lesions of the nucleus accumbens induced by 5,7-dihydroxytryptamine (5,7-DHT) on drug-induced circling were investigated in rats with unilateral nigrostriatal lesions induced by 6-hydroxydopamine (6-OHDA). Injections of 5-HT (60-120 micrograms in 1 microliter; 1 microliter/min) into the nucleus accumbens caused a significant decrease in the circling response to 5.0 mg/kg of d-amphetamine (s.c.). The distribution of radioactivity after intracerebral injections of [3H]5-HT using these parameters showed that although much of the injected material was retained in the nucleus accumbens there was also considerable spread to the frontal cortex. However, in further behavioural experiments, using an injection procedure (0.5 microliter; 0.11 microliter/min) which caused much greater retention of injected material in the nucleus accumbens, with minimal spread to the frontal cortex, the ability of 5-HT injected into the accumbens to block amphetamine-induced circling was not diminished. Moreover, injections of 5-HT into the frontal cortex did not have any effect on amphetamine-induced circling. Lesions of the nucleus accumbens induced by 5,7-DHT caused a significant enhancement of the contralateral circling response to 1.0 mg/kg of apomorphine and a similar but non-significant tendency to increase the circling responses to several other doses of apomorphine and amphetamine. The results provide evidence that serotonergic mechanisms in the nucleus accumbens inhibit circling behaviour generated by unilateral activation of nigrostriatal dopaminergic mechanisms.     

Modulation of dopamine function by glycine in the nucleus accumbens of the brain of the rat

The effects of glycine on the phasic changes in locomotor activity in the rat, caused by a persistent infusion of dopamine (DA) into the nucleus accumbens (ACB) were investigated. Dopamine (25 μg/24 hr), infused into the nucleus accumbens for 13 days, caused hyperactivity, with two peaks occurring on days 3–4 and 9–11. Glycine (12.5 or 25 μg/24 hr) infused into the nucleus accumbens on its own did not alter the locomotor activity, yet when infused at the same time as DA (25 μg/24 hr), glycine (12.5 or 25 μg/24 hr) inhibited the development of the first peak of hyperactivity induced by DA, with no effect on the second peak. A larger dose of glycine (50 μg/24 hr), infused alone, significantly increased locomotor activity, and a combination of this dose with DA (25 μg/24 hr), led to a temporal shift in the response to DA such that the first peak of hyperactivity was delayed to “fuse” with the second peak. The locomotor response to a threshold dose of DA (6.25 μg/24 hr) plus glycine (50 μg/24 hr) was no greater than could be accounted for by the hyperactivity response to glycine alone (50 μg/24 hr). Strychnine (10 μg/24 hr), infused into the nucleus accumbens, produced no alteration in locomotor activity. Similarly, when infused together with DA (25 μg/24 hr), strychnine (10 μg/24 hr) caused no significant alteration in the phasic hyperactivity induced by DA. However, strychnine (10 μg/24 hr), infused together with DA and glycine (25 and 12.5 μg/24 hr respectively), prevented the inhibition by glycine of the first peak of hyperactivity induced by DA. The results indicate that while glycine may not normally exert a tonic modulatory influence on those mechanisms in the nucleus accumbens which regulate locomotor activity, when applied exogenously glycine can partially moderate the locomotor response to DA, through an action on strychnine-sensitive receptors.     

Biphasic firing response of nucleus accumbens neurons elicited by THPB-18 and its correlation with DA receptor subtypes

AIM: To investigate the possibility whether THPB-18 (l-12-shloroscoulerine) possesses the D1 agonist-D2 antagonist action on meso-accumbens-mPFC DA system. METHODS: Single unit spontaneous firing activity was recorded in the nucleus accumbens (NAc) neurons of naive and unilateral-6-hydroxydopamine (6-OHDA)-lesioned Sprague-Dawley rats. The effects of drugs applied intravenously or iontophoretically were determined by thechange of firing rates. RESULTS: Under normal conditions, the systemic administration of THPB-18 produced a decrease-increase biphasic firing pattern in the NAc neurons during cumulative doses. High dose of THPB- 18 was capable of reversing the inhibition induced by both D2 agonist LY171555 and D1/D2 agonist APO on NAc firing activity. Spiperone pretreatment could not block the high dose of THPB-18-induced firing rate increase, which wasreversed by the D1 selective antagonist SCH23390. The tested NAc neurons were effectively inhibited byiontophoretically applied THPB- 18 in 90 % of 6-OHDA-lesioned rats, while THPB- 18 caused variable effects on thefiring of NAc neurons in the neurons of unlesioned rats. The inhibitory effect of THPB-18 was blocked byiontophoretic application of SCH23390, but not D2 antagonist spiperone. CONCLUSION: Similar to l-stepholidine,THPB-18 also possesses the “D1 agonistic-D2 antagonistic“ dual action on the VTA-NAc DA system.AIM: To investigate the possibility whether THPB-18 (l-12-shloroscoulerine) possesses the D1 agonist-D2 antago-nist action on meso-accumbens-mPFC DA system. METHODS: Single unit spontaneous firing activity was re-corded in the nucleus accumbens (NAc) neurons of naive and unilateral-6-hydroxydopamine (6-OHDA)-lesionedSprague-Dawley rats. The effects of drugs applied intravenously or iontophoretically were determined by thechange of firing rates. RESULTS: Under normal conditions, the systemic administration of THPB-18 produced adecrease-increase biphasic firing pattern in the NAc neurons during cumulative doses. High dose of THPB- 18 wascapable of reversing the inhibition induced by both D2 agonist LY171555 and D1/D2 agonist APO on NAc firingactivity. Spiperone pretreatment could not block the high dose of THPB-18-induced firing rate increase, which wasreversed by the D1 selective antagonist SCH23390. The tested NAc neurons were effectively inhibited byiontophoreticaUy applied THPB- 18 in 90 % of 6-OHDA-lesioned rats, while THPB- 18 caused variable effects on thefiring of NAc neurons in the neurons of unlesioned rats. The inhibitory effect of THPB-18 was blocked byiontophoretic application of SCH23390, but not D2 antagonist spiperone. CONCLUSION: Similar to l-stepholidine,THPB-18 also possesses the “D1 agonistic-D2 antagonistic“ dual action on the VTA-NAc DA system.     

Relationship between development of cross-sensitization to MK-801 and delayed increases in glutamate levels in the nucleus accumbens induced by a high dose of methamphetamine

Rationale The present study hypothesized that delayed increases in extracellular glutamate (Glu) levels in the nucleus accumbens (NAC), induced by a high dose of methamphetamine (METH), can result in some functional changes of excitatory amino acid receptors, developing behavioral cross-sensitization to a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801.Objectives The present study aims to examine whether two different doses of METH (2.5 and 1.0 mg/kg) induce different effects on the development of cross-sensitization to MK-801. To clarify the mechanisms for development and expression of cross-sensitization to MK-801, we measured extracellular Glu and dopamine (DA) levels in the NAC at METH injections in a treatment period and at MK-801 injection after a 12-day withdrawal period.Materials and methods METH- or MK-801-induced changes in Glu and DA levels and in locomotion were measured using in vivo microdialysis and infrared sensor, respectively.Results METH, at only 2.5 mg/kg, produced delayed increases in Glu levels and developed behavioral cross-sensitization to MK-801 (0.2 mg/kg). MK-801 (0.2 mg/kg) induced delayed increases in Glu levels in the NAC, but this time course was not completely consistent with MK-801-induced enhanced hyperlocomotion. During this time course, MK-801 (0.2 mg/kg) did not induce any changes in DA levels.Conclusions These results suggest that METH-induced, at 2.5 mg/kg, delayed increases in Glu levels are necessary for development of behavioral cross-sensitization to MK-801, but not METH. The enhanced locomotion-inducing effect of MK-801 might be related to some functional changes in excitatory amino acid receptors such as NMDA and dl-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid in the NAC.     

The contrasting effects of neuroleptics on transmitter release from the nucleus accumbens and corpus striatum

The effects of haloperidol, chlorpromazine and clozapine on transmitter release have been studied by measuring the simultaneous release of dopamine and acetylcholine from tissue slices of nucleus accumbens and striatum in vitro following in vivo drug application, either a single dose or daily for periods of up to 25 days. In the striatum, both single and chronic injections of haloperidol (1 and 2 mg. kg-1) caused a large and significant enhancement (up to 83%) of the K+-evoked release of [3H]acetylcholine synthesized from [3H]choline. In contrast, in the nucleus accumbens, the K+-evoked release of [3H]acetylcholine was not significantly affected by neuroleptics when compared with the controls which received injection of vehicle. Clozapine (50 mg.kg-1) also enhanced the K+-evoked release of [3H]acetylcholine relative to the resting release but the effect was smaller than that with haloperidol or chlorpromazine. The evoked release of preloaded [14C]dopamine from either nucleus accumbens or striatum was unaffected by treatment with haloperidol. However, chlorpromazine (25 mg.kg-1) and clozapine (50 mg.kg-1) significantly enhanced the evoked release of preloaded [14C]dopamine from tissue slices of striatum. A similar but reduced effect of enhancing release was also seen in the nucleus accumbens in response to chlorpromazine. In support of these results, dopamine itself applied in vitro induced an opposite effect to that of the neuroleptics. Thus in the striatum, dopamine (4 x 10(-4) M) markedly reduced the release of [3H]acetylcholine (45%). A smaller inhibition was also seen in the nucleus accumbens (25%).