左旋千金藤立定对溴隐亭诱导的哺乳期大鼠促乳素水平低下的拮抗作用

目的:研究左旋千金藤立定(SPD)对溴隐亭(Bro)诱导的促乳素(PRL)水平低下的对抗作用。方法:哺乳期母鼠sc Bro 0.5mg·kg~(-1)·d~(-1),PRL显著降低,乳腺组织发育不良,而且仔鼠体重增长缓慢。用放免法测定母鼠PRL,检查乳腺发育状况,评价SPD的对抗作用。结果:SPD30及100mg·kg~(-1)·d~(-1)ip,能够显著对抗Bro诱导的母鼠PRL降低,分娩后d15PRL为11±4及23±6μg·L~(-1)(生理盐水为7±2),而且乳腺组织发育正常,仔鼠在出生后d11—15内迅速生长发育。结论:SPD能阻断大鼠脑垂体前叶的D_2受体,是一个D_2受体的拮抗剂。     

睾酮诱导小鼠形成条件性位置偏爱和雌激素受体相关

目的:研究雌激素受体与睾酮诱导小鼠条件性位置偏爱的关系。方法:通过皮下注射睾酮训练小鼠形成条件性位置偏爱;在注射睾酮前注射雌激素受体拮抗剂ICI182780和他莫西芬,通过观察睾酮条件性位置偏爱的变化来判断雌激素受体是否在其中起作用。结果:0.5、1、2 mg.kg-1睾酮训练12 d,可以诱导小鼠产生条件性位置偏爱。雌激素受体拮抗剂ICI182780(2 mg.kg-1)或他莫西芬(1 mg.kg-1)可以抑制睾酮诱导的小鼠条件性位置偏爱。结论:睾酮具有奖赏效应,雌激素受体可能参与睾酮的奖赏效应。     

左旋千金藤立定增强mPFC DA受体对皮层下NAc DA释放的抑制作用(英文)

目的:研究左旋千金藤立定(SPD)激动内侧前额皮层(mPFC)D_1受体对皮层下伏隔核DA诱发释放的影响。方法:6-羟基多巴胺损伤大鼠mPFC两周后,同侧皮层内微量注射SPD,微透析检测电刺激中脑腹侧被盖区(VTA)或苯丙胺(AMP)诱导的NAc DA释放。结果:mPFC DA耗竭未改变NAc DA的基础水平和电刺激VTA诱发的DA释放,却明显易化AMP灌流诱发的NAc DA释放,表明mPFC DA系统参与调节NAc DA的诱发释放。mPFC内微量注射SPD未能改变电刺激VTA诱发的DA释放,但显著减弱AMP对NAc DA的诱发释放;该作用可被D_1拮抗剂Sch-23390部分翻转,而D_2拮抗剂spiperone无作用。结论:SPD强化mPFC D_1受体对皮层下伏隔核DA释放的抑制性调节作用。     

用位置偏爱法评价二氢埃托啡的精神依赖性潜力

本文报道应用条件性位置偏爱法,研究了DHE的精神依赖性的潜力及其与受体的关系。结果表明,DHE在1倍镇痛ED_(50)的剂量0.6μg·kg~(-1)sc下,就可产生明显的位置偏爱,且偏爱程度随药物剂量增加(3倍ED_(50),9倍ED_(50))而加强。但是DHE产生偏爱的受体机制可能与Mor不同,它不为M_(5050)(3 mg·kg~(-1)ip)所阻断。这些结果说明,DHE有较强的精神依赖潜力,而且在形成机制上,有其独特之处。     

左旋千金藤立定对大鼠血清中催乳素水平的影响(英文)

目的:观察左旋千金藤立定(SPD)对血清催乳素(PRL)水平的影响,研究SPD的药理作用。方法:成熟♀鼠ip多巴胺受体激动剂、拮抗剂或SPD后断头取血,然后用放射免疫法测定血清中的催乳素水平。结果:SPD引起血清PRL水平迅速而显著的增加,效应持续约1h,具有剂量依赖性。SPD的半数有效剂量为3.7mg·kg~(-1)(95％可信限为2.6—4.3mg·kg~(-1))。剂量为20mg·kg~(-1)时产 生最大效应,使血清PRL水平达到448±64μg·L~(-1),0.2mg·kg~(-1)则无效。对于多巴胺受体激动剂培高利特(pergolide)引起的PRL水平低下,SPD5mg·kg~(-1)有部分对抗作用,10mg·kg~(-1)能够完全对抗。结论:SPD是D_2多巴胺受体拮抗剂。     

培高利特对黑质多巴胺神经元放电活动的激动作用(英文)

目的:研究D_2受体激动剂培高利特(pergolide,Per)对大鼠黑质多巴胺(DA)神经元放电活动的影响,并与溴隐亭(bromocriptine,Bro)作比较,同时验证Per在整体动物有无D_1激动剂性质.方法:胞外单细胞电活动记录技术. 结果:二个药物均能抑制敏感及不敏感的DA神经元自发放电活动.Per的ID_(50)值为11.9μg kg~-1),而Bro为7.8 mg kg~(-1),Per比后者强很多.选择性D_2受体拮抗剂螺哌隆(spiperone,0.25 mg kg~(-1))或者选择性D_1受体拮抗剂Sch-23390(1—2 mg kg~(-1))可以减弱放电抑制.然而Bro引起的放电抑制并不都能为spiperone所减弱.结论:Per在整体动物有很强的D_2受体激动剂作用,比Bro强650倍.也有弱的D_1受体激动剂的性质.     

氯代斯阔任旋光异构体作用于多巴胺受体对动物行为的比较(英文)

目的:比较氯代斯阔任(CSL)旋光异构体对DA受体的作用特性。方法:采用小牛纹状体DA受体结合分析和小鼠、大鼠的行为实验。结果:d-CSL对D_1和D_2受体的K_i值分别是135和9150nmol·L~(-1),而l-CSL对D_1和D_2的亲和力(K_i)均为5.7nmol·L~(-1),分别为d-CSL的24倍和1605倍。dl-CSL对D_1和D_2受体的K_i值分别为8.9和9.6nmol·L~(-1),比l-CSL稍弱。大鼠刻板活动和木僵实验、小鼠的跳跃和自发活动实验均证明CSL旋光异构体对DA受体有阻滞作用。结论:CSL旋光异构体为DA受体阻滞剂的作用特性,其作用强度为:l-CSL>dl-CSL>>d-CSL。     

吗啡抑制程序诱导的大鼠烦渴行为

目的:观察吗啡对程序诱导的烦渴行为(schedule-induced polyipsia,SIP)的影响。方法:在每天2.5h实验期内,通过程序性供应食物(固定时间60s)诱导限食大鼠建立SIP行为。结果:对于已建立稳定SIP行为的大鼠,实验前30min sc吗啡(3.0,10.0mg·kg~(-1)明显减弱大鼠的SIP行为。连续吗啡慢性处理(10.0mg·kg~(-1),sc)5d,停药后d3大鼠的SIP行为无显著性变化。实验前60min侧脑室、伏隔核、腹侧被盖分别给予吗啡(5μg)可明显抑制大鼠的SIP行为。结论:SIP行为具有奖赏行为的特征,吗啡抑制SIP行为可能与奖赏效应的替代有关。     

介导单针吗啡诱导行为敏化新的脑区——隔核

目的单针吗啡诱导的行为敏化是研究阿片类药物成瘾神经可塑性变化的重要动物模型。目前认为隔核是脑内与奖赏、学习和记忆等关系较为密切的核团之一。因此,本研究将探讨隔核在单针吗啡诱导的行为敏化中的作用,并初步解析其作用机制。方法和结果通过旷场实验发现,单针吗啡(第1天:3～-30 mg·kg-1,sc)预处理的大鼠在吗啡(第8天:3 mg·kg-1,sc)激发时表现出高活动性,也就是行为敏化反应;在敏化实验前进行双侧隔核电损毁手术,发现大鼠对吗啡的行为敏化反应消失,但对吗啡的急性反应不受影响;而在单针吗啡预处理之后立即进行双侧隔核电损毁,发现7 d后大鼠在吗啡激发时仍表现出行为敏化;此外,通过条件性位置偏爱实验和甩尾实验,分别评价了吗啡在隔核损毁大鼠中的奖赏与镇痛作用;为了进一步明确隔核参与行为敏化的过程,按照侧隔核与中隔核的分区,分别通过核团内微量注射吗啡的方法建立行为敏化。发现预处理时在侧隔核或中隔核给于吗啡(30μg/rat)能使大鼠在激发后(3mg·kg-1,sc)出现行为敏化;预处理前,在侧隔核或中隔核内给与利多卡因(10μg/rat)或mu受体拮抗剂β-FNA(2μg/rat)能抑制行为敏化的建立。结论在吗啡预处理前,隔核损毁或者阻断隔核内阿片受体能抑制行为敏化的建立,说明隔核是参与单针吗啡诱导行为敏化形成期的关键性核团,并且侧隔核与中隔核的mu受体可能是这一过程的作用靶点。     

多巴胺诱导大鼠海马脑片Ca~(2 )-钙调素依赖性蛋白激酶Ⅱ活性的抑制作用(英文)

目的:研究多巴胺(DA)对大鼠海马脑片Ca~(2 )-钙调素依赖性蛋白激酶Ⅱ(CCDPK Ⅱ)活性的影响。方法:采用大鼠海马脑片体外培养模型,以~(32)P-掺入法测定CCDPK Ⅱ的活性。结果:外源性DA可显著降低大鼠海马脑片CCDPK Ⅱ活性,并有一定的浓度依赖性和时间依赖性。去除胞外的Ca~(2 )对不同浓度DA诱导的CCDPK Ⅱ活性抑制有部分或完全保护作用。阿扑吗啡(非特异性DA受体激动剂)、SKF38393(特异性D_1样DA受体激动剂)和喹吡罗(特异性D_2样DA受体激动剂)均可显著降低CCDPK Ⅱ的活性。Sch-23390(特异性D_1样DA受体拮抗剂)和多潘立酮(特异性D_2样DA受体拮抗剂)均可拮抗DA所诱导的酶活性抑制。结论:DA抑制海马CCDPK Ⅱ的活性,其作用机制与D_1样和D_2样受体以及胞外Ca~(2 )的内流有关。     

In vivo assessment of release and metabolism of dopamine in the ventrolateral striatum of awake rats following administration of dopamine D1 and D2 receptor agonists and antagonists

The ability of specific dopamine (DA) receptor agonists and antagonists to modify the release and metabolism of DA in the ventrolateral striatum of awake rats was assessed using in vivo microdialysis. The specific DA D₂ receptor antagonist, raclopride (0.1, 0.5 and 2.0mg/kg, i.p.), dose-dependently increased release of DA and levels of the metabolites DOPAC and HVA, while the D₂ receptor agonist, quinpirole (0.03, 0.1 and 0.3 mg/kg), decreased levels of DA, DOPAC and HVA. The DA D₁ receptor antagonist, SCH23390 ([R + (+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-o]) (0.01, 0.05 and 0.25 mg/kg), produced an increase in DA, DOPAC and HVA but of a lesser magnitude than raclopride. The D₁ agonist SKF38393 (1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol) (1.0, 3.0 and 10.0 mg/kg) failed to affect the release of metabolism of DA at any dose. These results support previous findings that activation of D₂ receptors has greater control over in vivo DA function, than drugs specifically affecting D₁ 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.     

A pharmacological study of dopaminergic receptors in planaria

The dopaminergic receptors of planaria have been studied with pharmacological and biochemical criteria. Dopamine D₁ selective agonists (CY 208243 (10 μg/ml) and SKF 38393 (10 μg/ml)) induced in planaria typical screw-like hyperkinesias, that were inhibited by a D₁ antagonist (SCH 23390 (10 μg/ml)), but not by a D₂ antagonist (sulpiride (1000 μg/ml)). Dopamine D₂ selective agonists (PHNO (5 μg/ml), lisuride (5 μg/ml)) on the contrary induced a typical “C” like curling, that was inhibited by pretreatment with D₂ selective blocking agents, but not by D₁ selective blocking agents. With agonists with a D₁ /D₂ mixed action (apomorphine 60 μg/ml) or with amphetamine (100 μg/ml), the D₁ type movements appeared to be more evident.

Dopamine D₁-selective agonists, mixed action agonists or D₂-selective agonists, all induced a significant increase in levels of cAMP, that was prevented by pretreatment with the specific DA blocking agent.     

Dopamine Receptor Mediation of the Exploratory/Hyperactivity Effects of Modafinil

Modafinil (2-((diphenylmethyl)sulfinyl)acetamide) is described as an atypical stimulant and is a putative cognition enhancer for schizophrenia, but the precise mechanisms of action remain unclear. Receptor knockout (KO) mice offer an opportunity to identify receptors that contribute to a drug-induced effect. Here we examined the effects of modafinil on exploration in C57BL/6J mice, in dopamine drd1, drd2, drd3, and drd4 wild-type (WT), heterozygous (HT), and KO mice, and in 129/SJ mice pretreated with the drd1 antagonist {"type":"entrez-protein","attrs":{"text":"SCH23390","term_id":"1052733334","term_text":"SCH23390"}}SCH23390 using a cross-species test paradigm based on the behavioral pattern monitor. Modafinil increased activity, specific exploration (rearing), and the smoothness of locomotor paths (reduced spatial d) in C57BL/6J and 129/SJ mice (increased holepoking was also observed in these mice). These behavioral profiles are similar to that produced by the dopamine transporter inhibitor GBR12909. Modafinil was ineffective at increasing activity in male drd1 KOs, rearing in female drd1 KOs, or reducing spatial d in all drd1 KOs, but produced similar effects in drd1 WT and HT mice as in C57BL/6J mice. Neither dopamine drd2 nor drd3 mutants attenuated modafinil-induced effects. Drd4 mutants exhibited a genotype dose-dependent attenuation of modafinil-induced increases in specific exploration. Furthermore, the drd1 KO effects were largely supported by the {"type":"entrez-protein","attrs":{"text":"SCH23390","term_id":"1052733334","term_text":"SCH23390"}}SCH23390 study. Thus, the dopamine drd1 receptor appears to exert a primary role in modafinil-induced effects on spontaneous exploration, whereas the dopamine drd4 receptor appears to be important for specific exploration. The modafinil-induced alterations in exploratory behavior may reflect increased synaptic dopamine and secondary actions mediated by dopamine drd1 and drd4 receptors.     

Contributions of cysteine 114 of the human D3 dopamine receptor to ligand binding and sensitivity to external oxidizing agents

1. Cysteine 114 (C114) of the human dopamine D3 receptor is located at the helical face of transmembrane segment III (TMIII) near aspartate 110, a counterion for the amine group of catecholamines. The contributions of C114 to receptor function were investigated here using site-directed mutagenetis of C114 to serine.
2. The C114S mutant, as expressed in Sf-9 cells, bound aminotetralin antagonists (UH-232 and AJ-76) and several agonists ((−)3-PPP, apomorphine, pramipexole and quinpirole) with markedly lower affinities as compared to the wild type D3 receptor, but bound other structurally diverse dopaminergic ligands with only minor changes in affinity. Because an N-propyl substituent is the only common structural feature among most affected ligands, we propose that the mutation alters `a propyl cleft'' on the receptor. The mutation hardly affected quinpirole-dependent [³⁵S]-GTPγS binding, suggesting C114 plays a minimal role in receptor-G-protein coupling.
3. N-Ethylmaleimide(NEM), a sulfhydryl modifying agent, blocked ligand binding to the D3 receptor, but not to the C114S mutant. We infer that C114 is the primary residue on the D3 receptor vulnerable to external oxidizing agents. Dopamine D2long and D4₂ receptors contain highly homologous TMIII sequences including an equivalent cysteine residue. However, only the D2long receptor, not the D4₂ receptor, displayed NEM sensitivity similar to that of the D3 receptor.
4. We conclude that C114 is critical for high affinity interactions between the D3 receptor and ligands containing an N-propyl substituent, and unlike its counterpart in the D4₂ receptor, is highly susceptible to external oxidizing agents.

     

多巴胺受体系统在诱发产生的大麻酚类戒断症状中不起主要作用(英文)

AIM: To determine the dopaminergic systeminvolvement in precipitated cannabinoid withdrawalsyndrome. METHODS: The dopamine D_1 receptorantagonist SCH23390 or the dopamine D_2 receptorantagonost sulpiride was administered to rats chronicallytreated with either △~9-tetrahydrocannabinol (THC) orvehicle. Subjects were then injected with eitherSR141716A or vehicle and behavior was observed for1 h. RESULTS: Administration of the cannabinoidreceptor antagonist SR141716A to animals chronicallytreated with THC as described by Tsou et al (1995)     

特麦角脲对海洛因自身给药大鼠部分脑区多巴胺D2受体及强啡肽蛋白与基因表达的影响

目的探讨特麦角脲治疗海洛因依赖的作用机制。方法成年雄性SD大鼠,随机分为正常对照组、海洛因依赖形成期生理盐水干预组、海洛因依赖形成期特麦角脲干预组、复发期生理盐水干预组和复发期特麦角脲干预组;除正常对照组外,其余4组分别建立海洛因静脉自身给药和线索诱发复发模型,干预后灌注固定,留取各脑区切片,采用免疫组化和原位杂交技术,分别检测各脑区多巴胺D2受体蛋白和mRNA、强啡肽原蛋白、前强啡肽原mRNA表达水平。结果伏核多巴胺D2受体蛋白在海洛因依赖形成期表达下调,在复发期表达上升,多巴胺D2受体基因表达与蛋白表达基本一致,特麦角脲可使复发期受体蛋白表达回降。杏仁核中央核多巴胺D2受体蛋白和基因表达在复发期上调,特麦角脲可使基因表达回降。前额叶多巴胺D2受体蛋白和基因表达在形成期上调,蛋白表达在复发期下调,特麦角脲使复发期基因表达下调。伏核强啡肽蛋白和基因在复发期表达上调,特麦角脲使之回降。杏仁核中央核强啡肽蛋白在复发期表达上调,特麦角脲使之回降。结论海洛因依赖形成期中脑边缘系统多巴胺活动升高,复发期活动降低,特麦角脲对此有双向调节作用。复发期强啡肽活动上升,特麦角脲可使之降低,有治疗海洛因滥用的潜力。     

Dopamine D2-like receptors and amino acid-induced glomerular hyperfiltration in humans

AIMS: In rodents, blockade of dopamine D2-like receptors abolishes both the physiological increase in glomerular filtration rate (GFR) induced by amino acids and the pathological hyperfiltration in experimental diabetes mellitus. This study addressed the contribution of dopamine D2-like receptors to changes in renal haemodynamics after amino acid infusion in humans. METHODS: Twelve healthy volunteers participated in this double-blind, randomized, cross-over study. GFR and renal blood flow (RPF) were assessed by renal clearance of inulin and p-aminohippuric acid (PAH), respectively. Following infusion of 0.45% saline at baseline, an electrolyte-balanced solution of mixed amino acids (10%) was infused. Prior to the experiments, the subjects received orally either placebo, or sulpiride (10 mg kg-1), a centrally and peripherally acting D2-like receptor antagonist, or domperidone (1 mg kg-1) which affects only peripheral D2-like receptors. RESULTS: In the placebo series, amino acid infusion significantly increased GFR and RPF by up to 15.8 +/- 5.3% and 14.4 +/- 6.1%, respectively, while mean blood pressure and heart rate remained unchanged. Pretreatment with domperidone only marginally altered the renal response to amino acids (maximal increase by 13.2 +/- 5.6 and 11.9 +/- 4.0% in GFR and RPF, respectively), while sulpiride completely abolished the renal haemodynamic changes induced by amino acids. Total and fractional urinary sodium excretion as well as urinary osmolality were similar at baseline and increased in response to amino acids, to the same extent, in all series. No changes in renal dopamine excretion occurred. CONCLUSION: The results indicate that in man dopamine D2-like receptors are involved in the renal haemodynamic response to amino acid infusion. Whether dopamine D2-like receptor blockade diminishes glomerular hyperfiltration in pathological states requires clinical investigations.     

Similar binding of 3H-ADTN and 3H-apomorphine to calf brain dopamine receptors.

The binding of 3H(+/-)-ADTN (of high specific activity; 7.6 Ci/mmole) to homogenates of calf striatum was investigated. The dissociation constant (KD) for the specific, saturable binding of 3H-(+/-)-ADTN was 1 nM and the density of specific sites was 100 fmoles/mg protein. The IC50 values (nM concentrations inhibiting specific binding by 50%) were 0.9 for (+/-)-N-propyl-norapomorphine, 3.0 for dopamine, 7 for (--)-adrenaline, 60 for (--)-noradrenaline and 4000 for isoproterenol, a series of potencies compatible with properties for a dopaminergic site. The (+)-enantiomer of ADTN was 10 times more potent than (--)-ADTN in competing for 3H-(+/-)-ADTN, while the (--)-enantiomer of 5-OH-dipropyl-ATN was 40 times more potent than the (+)-isomer. The IC50 values for various agonists against 3H-(+/-)-ADTN were similar to those against 3H-apomorphine or 3H-dopamine in the calf striatum. A comparison of these 3H-(+/-)-ADTN data to those for 3H-spiperone suggests that the two 3H-ligands label different receptor sites.     

Role of genotype and dopamine receptors in behaviour of inbred mice in a forced swimming test

The role of genotype in the effects of selective D1 and D2 dopamine agonists and antagonists on behavioural despair (Porsolt's test) was studied. Mice of nine inbred strains showed significant interstrain differences in duration of immobility. The influence of dopaminergic drugs was assessed in six strains characterized by different levels of swimming activity. SKF 38393 (10 mg/kg), an agonist at D1 dopamine receptors, increased swimming activity, while the D1 antagonist SCH 23390 (0.2 and 0.5 mg/kg) reduced it, the effects being genotype dependent. The involvement of D2 dopamine receptors in the regulation of mouse behaviour in the forced swimming test was not so evident; the D2 agonist bromocriptine (10 mg/kg) produced no significant effect. The D2 agonist quinpirole (2.5 mg/kg) increased immobility in the majority of the mouse strains studied, while in CBA mice it resulted in a marked reduction of immobility. The D2 antagonist sulpiride (20 mg/kg) decreased immobility and increased active swimming only in two strains. The present results suggest a different role for D1 and D2 dopamine receptors in the regulation of swimming in the mouse.