遗传性小脑共济失调一家系5例报告

本文报告遗传性小脑共济失调一家3代5人发病者. 例1为先证者,女,40岁,农民,病史6年.该患者于34岁起渐现走路不稳易跌,语言含糊不清,双手笨拙及饮水呛咳,吞咽困难,进行性加重.查体:步态蹒跚,吟诗样语言,双眼球水平震颤,双手意向性震颤,四肢肌张力增高,四肢肌力V级,双侧指鼻及跟膝胫试验阳性,昂白征阳性.深浅感觉正常,双侧巴彬斯基氏征阳性.头部MRI检查示"小脑沟增宽加深,提示小脑萎缩".临床诊断为遗传性小脑共济失调.例2为先证者大姐,现年45岁,32岁起病,行走困难,多数时间卧床,偶能扶墙行走,生活不能完全自理.例3为先证者妹妹,现年37岁,31岁起病,步态不稳,蹒跚步态,语言含糊不清,生活能自理.例4为先证者母亲,40岁起病,56岁死于该病.先证者父亲,现年67岁,正常.例5为先证者大姐女儿,现年26岁,近1年来自觉双下肢活动不灵,查体:双眼球可见水平震颤,双下肢肌张力略增高,腱反射活跃,双侧巴彬斯基氏征阳性.     

5-羟色胺受体拮抗剂预防丙泊酚注射痛有效性和安全性的Meta分析

目的系统评价5-羟色胺（5-HT3）受体拈抗剂预防丙泊酚注射痛的有效性和安全性。方法计算机检索PubMed、EMbase、TheCochraneLibrary（2012年第1期）、CNKI、CBM、VIP和WanFangData,查找有关5-HT3受体拈抗剂预防丙泊酚注射痛的随机对照试验（RCT）,检索时限均从建库至2012年9月。由2位研究人员按照纳入和排除标准独立筛选文献、提取资料和评价质量后,然后采用RevMan5．2软件进行Meta分析。结果最终纳入15个RCT,共l413例患者。Meta分析结果显示：①5-HT,组丙泊酚注射痛发生率明显小于对照组[RR=0．14,95％CI（0．09,0．21）,P〈0．00001];②在疼痛程度方面,两组轻度注射痛差异无统计学意义[RR=0．84,95％CI（0．56,1．26）,P=0．39];5-HT,组丙泊酚中度注射痛[RR=0．25,95％CI（0．19,0．34）,P〈0．00001]和重度注射痛的发生率[RR=0．16,95％CI（0．10,0．24）,P〈0．00001]均明显低于对照组。③在术后不良反应方面,5-HT3组术后恶心和呕吐fRR：0．19,95％CI（0．11,0．34）,P〈0．00001]及寒颤[RR=0．20,95％CI（0．12,0．33）,P〈0．00001]的发生率均明显少于对照组。结论5-HT3受体拮抗剂能有效预防丙泊酚注射痛,且能减轻丙泊酚注射的疼痛程度和术后不良反应发生率。受纳入研究的数量和质量限制,上述结论尚待开展更多高质量研究加以验证。     

5-羟色胺2A受体基因与疾病的关系

5 羟色胺 (5 HT)既是神经递质 ,又是血管活性物质 ,在中枢神经系统和周围组织中发挥着多种生理功能 ,例如对心血管、呼吸、体温、睡眠、摄食行为、情绪反应、下丘脑神经激素分泌和平滑肌张力的调节等。分子学研究揭示 ,多种编码 5 羟色胺 2A受体 (5 HT2AR)蛋白质的基因表现出多态性 ,这种多态性在许多情况下改变了它们对神经递质和特定药物的敏感性。因此 ,不同的受体基因型可能对疾病的易感性也不同 ;对不同的个体使用同一剂量的药物 ,其临床效应也可能不同。本文对近年来有关 5 HT2AR基因与多种疾病关系的研究进展综述如下。1　 …     

5-羟色胺2A受体基因多态性与精神疾病患者自杀未遂的关联性研究

目的　探讨 5 -羟色胺 2A(5- HT2A)受体基因A 14 3 8G、T10 2C多态性与精神疾病患者的自杀未遂之间的关系。方法　对 5 2例有自杀未遂的精神疾病患者和 64例无自杀的精神疾病患者及 63例正常人 ,按常规方法提取DNA ,用限制性片段长度多态性方法分析 5 - HT2A受体基因的多态性。结果　 5 -HT2A受体基因A 14 3 8G和T10 2C两位点多态性呈完全连锁不平衡 ;自杀未遂组的A 14 3 8G、T10 2C多态性位点的T/G等位基因频率高于正常对照组 (P <0 . 0 5 ) ,自杀未遂组与正常对照组间的基因型分布的差异也有显著性 (P <0 . 0 5 )。结论　精神疾病患者的自杀未遂与 5 - HT2A受体基因的A -14 3 8G、T10 2C多态性有关 ,T/G等位基因可能是自杀行为的危险因素。     

中国人群5-羟色胺2A受体基因启动子区-1438A／G多态性与摄食障碍的关系

目的：研究5-羟色胺2A受体(serqotonin 2A receptor，5-HT2AR)基因多态性与摄食障碍的关联分析。方法：引用德国SIAB摄食调查问卷量表作为评定标准，2003-06／12从武汉、宜昌4所学校的1000名初、高中学生中筛查出50例存在摄食问题的学生组成可能摄食障碍组，与可能摄食障碍组相匹配的50例作为正常对照组，比较两组间5-HT2AR基因启动子区-1438G／A基因型和等位基因频率；比较两组间汉密尔顿焦虑量表、抑郁量表得分结果。结果：两组间5-HT2AR基因启动子区-1438G／A多态性在两组间差异无显著性意义；汉密尔顿焦虑、抑郁量表得分差异存在显著性意义，其中可能摄食障碍组分别为(14．45&;#177;4．84)，(11．95&;#177;2．87)分，对照组分别为(4．75&;#177;2．22)，(3．20&;#177;1．40)分（P&;lt;0．05)。结论：5-HT2AR基因启动子区一14．38G／A多态性与摄食障碍无相关性、出现摄食问题的人群有明显的情绪问题。     

5-羟色胺2A受体基因多态性与品行障碍的相关性

目的:探讨5-羟色胺2A(5-HT2A)受体基因A1438G、T102C多态性与品行障碍(CD)的相关性.方法:对88例病例组和60例对照组提取基因组DNA,采用RFLP技术分析相应的基因型,并比较两组不同基因型的行为特点有无差异.结果:5-HT2AA1438G基因型和等位基因频率在病例组和对照组之间差异无显著性(P＞0.05),5-HT2AT102C多态性分析虽未发现其与品行障碍存在显著关联,但伴ADHD组的T1/T1基因型频率明显低于对照组,T1/T2基因型频率明显高于对照组,差异有显著性(P＜0.05).结论:5-HT2A受体基因的A1438G、T102C多态性与品行障碍的关系尚需进一步探讨.     

中国人群5-羟色胺2A受体基因启动子区-1438A/G多态性与摄食障碍的关系

目的:研究5-羟色胺2A受体(serotonin2Areceptor,5-HT2AR)基因多态性与摄食障碍的关联分析。方法:引用德国SIAB摄食调查问卷量表作为评定标准,2003-06/12从武汉、宜昌4所学校的1000名初、高中学生中筛查出50例存在摄食问题的学生组成可能摄食障碍组,与可能摄食障碍组相匹配的50例作为正常对照组,比较两组间5-HT2AR基因启动子区-1438G/A基因型和等位基因频率;比较两组间汉密尔顿焦虑量表、抑郁量表得分结果。结果:两组间5-HT2AR基因启动子区-1438G/A多态性在两组间差异无显著性意义;汉密尔顿焦虑、抑郁量表得分差异存在显著性意义,其中可能摄食障碍组分别为(14.45±4.84),(11.95±2.87)分,对照组分别为(4.75±2.22),(3.20±1.40)分(P<0.05)。结论:5-HT2AR基因启动子区-1438G/A多态性与摄食障碍无相关性。出现摄食问题的人群有明显的情绪问题。     

核心家系5-羟色胺2A受体T102C多态性与精神分裂症的关联性

背景：精神分裂症是一种常见的病因未明的精神病．是世界各国重点研究课题，其遗传学尤其是分子遗传学研究近来较受瞩目，其中对相关候选功能基因的研究显示出较好的前景。 目的：分析5-羟色胺2A受体基因多态性与精神分裂症的相关性。 设计：以诊断为依据的病例观察，关联性分析。 单位：新乡医学院第二附属医院及中原油田总医院13分院。 对象：患者组为2003-08／2004-04在新乡医学院第二附属医院住院的精神分裂症先证者56例，父母组为患者组的健康双亲112名。 方法：采用聚合酶链式反应方法（PCR-RFLP）对符合精神分裂症（CCMD-3）诊断标准的56个先证者及其父母组成的核心家系进行检测．并对5-羟色胺2A受体基因分型，精神分裂症的5-羟色胺2A受体T102C多态性运用传递不平衡（TDT）检验。 主要观察指标：5-羟色胺2A受体基因的等位基因、基因型频率分布与H-W吻合度检验结果及5-羟色胺2A受体基因的分析结果。 结果：56例患者及其父母112名全部采集到各项指标，均进入结果分析。①患者组与父母组的基因型频数差异无显著性意义（X^2=4．423．P=0．110）．等位基因分布差异亦无显著性意义（X^2=1．147．P=0．563），Hardy-Weinberg平衡吻合度良好。②在56个家系中．采用传递不平衡检验考察39个父亲或母亲为杂合子基因型的核心家系的传递不平衡性，显示精神分裂症与5-羟色胺2A受体基因无显著关联（X^2．703,P=0．10）。结论：5-羟色胺2A受体基因T102C在中国汉族人群中与精神分裂症无关联。     

多巴胺受体与5-羟色胺2A受体基因多态性与迟发性运动障碍的关联

目的：观察分析多巴胺D2受体基因TaqIA多态性、多巴胺D3受体基因Ser9GIy功能多态性、5-羟色胺2A受体基因A-1438G、T102C多态性与精神分裂症伴发迟发性运动障碍的相关性。方法：于2000-10／2001-11选择江苏省扬州五台山医院长期住院的符合CCMD-2-R精神分裂症的诊断标准的籍贯江苏省的男性精神分裂症患者94例为观察对象。患者住院时间至少8年以上。在住院期间一直服用第一代抗精神病药物。并使用异常不自主运动量表评定精神分裂症患者有无迟发性运动障碍，异常不自主运动量表总分≥3分（躯体有一处≥3分，躯体有两处或多处等于2分）即可诊断为迟发性运动障碍；量表评定先后于半年内进行3次，3次异常不自主运动量表评分均大于3分者为迟发性运动障碍患者。其中迟发性运动障碍者42例，非迟发性运动障碍者52例。常规氯仿一饱和酚白细胞提取法提取DNA，引导引物和折返引物的合成、PCR的反应条件及扩增产物经MspI限制性内切酶消化方法参考文献进行。应用聚合酶链反应-限制性片段长度多态性法分析两组多巴胺D2受体基因TaqIA多态性、多巴胺D3受体功能基因Ser9Gly多态性、5-羟色胺2A受体基因A-1438G、T102C多态性位点的等位基因频率和基因型分布。结果：94例患者的各项指标均测得，全部进入结果分析。①两组患者的多巴胺D2受体基因TaqIA多态性位点的等位基因频率和基因型分布差异无显著性意义[X^2=0．19，P〉0．05）；（r=0.51，P〉0．05）]。②两组患者多巴胺D3受体基因Ser9Gly多态性基因型和等位基因频率的分布差异无显著性意义[0（2=4．98，P=0．08）；（r=0.84，P〉0．05）1。③5-羟色胺2A受体基因T102C多态性位点与A-1438G为完全连锁不平衡，迟发性运动障碍组与非迟发性运动障碍组的基因型总体分布的差异无显著性意义（X^2=4．37，P〉0．05），等位基因频率分布的差异有显著性意义[（等位基因A54／64．3，50／49．1），（等位基因G30／35．7，52／50．9），r=4．36，P〈0．05]。结论：在中国汉族男性精神分裂症患者中多巴胺D2受体基因的TaqIA多态性、多巴胺D3受体功能基因的Ser9Gly多态性可能不是影响迟发性运动障碍发生的主要危险因素。5-羟色胺2A受体基因的T102C、A-1438G多态性可能与男性精神分裂症患者的迟发性运动障碍相关联。     

多巴胺受体与5-羟色胺2A受体基因多态性与迟发性运动障碍的关联

目的:观察分析多巴胺D2受体基因TaqIA多态性、多巴胺D3受体基因Ser9Gly功能多态性、5-羟色胺2A受体基因A-1438G、T102C多态性与精神分裂症伴发迟发性运动障碍的相关性。方法:于2000-10/2001-11选择江苏省扬州五台山医院长期住院的符合CCMD-2-R精神分裂症的诊断标准的籍贯江苏省的男性精神分裂症患者94例为观察对象。患者住院时间至少8年以上。在住院期间一直服用第一代抗精神病药物。并使用异常不自主运动量表评定精神分裂症患者有无迟发性运动障碍,异常不自主运动量表总分≥3分(躯体有一处≥3分,躯体有两处或多处等于2分)即可诊断为迟发性运动障碍;量表评定先后于半年内进行3次,3次异常不自主运动量表评分均大于3分者为迟发性运动障碍患者。其中迟发性运动障碍者42例,非迟发性运动障碍者52例。常规氯仿-饱和酚白细胞提取法提取DNA,引导引物和折返引物的合成、PCR的反应条件及扩增产物经MspI限制性内切酶消化方法参考文献进行。应用聚合酶链反应-限制性片段长度多态性法分析两组多巴胺D2受体基因TaqIA多态性、多巴胺D3受体功能基因Ser9Gly多态性、5-羟色胺2A受体基因A-1438G、T102C多态性位点的等位基因频率和基因型分布。结果:94例患者的各项指标均测得,全部进入结果分析。①两组患者的多巴胺D2受体基因TaqIA多态性位点的等位基因频率和基因型分布差异无显著性意义犤(χ2=0.19,P>0.05);(χ2=0.51,P>0.05)犦。②两组患者多巴胺D3受体基因Ser9Gly多态性基因型和等位基因频率的分布差异无显著性意义犤(χ2=4.98,P=0.08);(χ2=0.84,P>0.05)犦。③5-羟色胺2A受体基因T102C多态性位点与A-1438G为完全连锁不平衡,迟发性运动障碍组与非迟发性运动障碍组的基因型总体分布的差异无显著性意义(χ2=4.37,P>0.05),等位基因频率分布的差异有显著性意义犤(等位基因A54/64.3,50/49.1),(等位基因G30/35.7,52/50.9),χ2=4.36,P<0.05犦。结论:在中国汉族男性精神分裂症患者中多巴胺D2受体基因的TaqIA多态性、多巴胺D3受体功能基因的Ser9Gly多态性可能不是影响迟发性运动障碍发生的主要危险因素。5-羟色胺2A受体基因的T102C、A-1438G多态性可能与男性精神分裂症患者的迟发性运动障碍相关联。     

Acute Cerebellar Ataxia in COVID-19 Infection: A Case Report

BackgroundThe outbreak of coronavirus disease 2019 (COVID-19) has been widely reported to cause symptoms such as fever, cough, sore throat, fatigue, and shortness of breath. Neurologic complications have not been widely reported without associated respiratory symptoms. These neurologic manifestations have been found mostly in the elderly. There has been no report of ataxia or COVID-19 cerebellitis in the young adult population without associated respiratory symptoms.Case ReportHere we report the case of a 30-year-old patient who presented with isolated cerebellar symptoms and was diagnosed with COVID-19 cerebellitis.Why Should an Emergency Physician Be Aware of This?It is important for emergency physicians to know that COVID-19 can have many clinical manifestations and to have a high level of suspicion with acute neurologic symptoms.     

青年男性亚急性小脑性共济失调的罕见病因

亚急性小脑性共济失调多见于非典型感染、自身免疫性疾病和副肿瘤性小脑变性。本文报道1例表现为亚急性小脑性共济失调患者,其病因罕见。该患者男性,31岁,亚急性起病,临床表现为小脑性共济失调,严重免疫抑制状态,经筛查发现人类免疫缺陷病毒(human immunodeficiency virus, HIV)抗体及核酸均阳性、脑脊液JC病毒DNA阳性,临床诊断为JC病毒小脑颗粒细胞神经元病,经抗逆转录病毒治疗后共济失调症状好转,3个月后随访症状稳定。JC病毒小脑颗粒细胞神经元病是一种JC病毒感染引起的新型临床症候,目前报道较少,本例为国内首次报道。本病例提示HIV感染免疫抑制患者出现共济失调时需筛查JC病毒,免疫功能的恢复有助于控制JC病毒小脑颗粒细胞神经元病症状进展。     

5-HT1B Receptor Polymorphism and Clinical Response to Sumatriptan

The 5-HT₁ receptor agonist, sumatriptan, is highly effective in the treatment of migraine. Some patients, however, do not respond or experience recurrence of the headache. In addition, some patients report chest symptoms after sumatriptan. We investigated whether these different responses could be attributed to genetic diversity of the 5-HT_1B receptor, which most likely mediates the therapeutic action and the coronary side effects of sumatriptan. Allele frequencies of two polymorphisms in the 5-HT_1B receptor gene ( G861C and T-261G ) were investigated in migraine patients with consistently good response to sumatriptan (n=14), with no response (n=12), with recurrence of the headache (n=12), with chest symptoms (n=13), and in patients without chest symptoms (n=27). Allele frequencies (G:0.74; C:0.26 at nt 861 and T:0.39; G:0.61 at nt -261) did not differ between patient groups, indicating that genetic diversity of the 5-HT_1B receptor does not seem to be involved in the different clinical responses to sumatriptan.     

Pharmacology of the Selective 5-HT1B/1D Agonist Frovatriptan

Objective.—To determine the pharmacological profile of frovatriptan.
Background.—Frovatriptan is a new 5-HT_1B/1D agonist developed for the treatment of migraine.
Methods.—Pharmacological studies were performed using in vitro and in vivo techniques.
Results.—Radioligand-binding studies showed that frovatriptan has a high affinity for 5-HT_1B and 5-HT_1D receptors, and moderate affinity for 5-HT_1A, 5-HT_1F, and 5-HT₇ receptors. In vitro, frovatriptan acts as a potent full agonist at human cloned 5-HT_1B and 5-HT_1D receptors, and as a moderately potent full agonist at 5-HT₇ receptors. Studies of frovatriptan in isolated human arteries demonstrated a lower threshold for constriction of cerebral than coronary vasculature and a bell-shaped dose-response curve was apparent in the coronary arteries. In anesthetized dogs, frovatriptan administration produced no measurable effect on cardiac function or on blood pressure. Frovatriptan had no effects on coronary blood flow following transient coronary artery occlusion, whereas sumatriptan produced a prolonged and significant decrease in coronary blood flow.
Conclusion.—The pharmacology of frovatriptan suggests that it should be an effective agent for the acute treatment of migraine, with a low potential for undesirable peripheral effects.     

5-Hydroxytryptamine(1B/1D) and 5-hydroxytryptamine1F receptors inhibit capsaicin-induced c-fos immunoreactivity within mouse trigeminal nucleus caudalis

In order to investigate the c-fos response within the trigeminal nucleus caudalis (Sp5C) after noxious meningeal stimulation, capsaicin (0.25, 0.5, 1 and 5 nmol) was administered intracisternally in urethane (1 g/kg) and alpha-chloralose (20 mg/kg) anaesthetized male mice. Capsaicin induced a robust and dose-dependent c-fos-like immunoreactivity (c-fos LI) within Sp5C. C-fos LI was observed within laminae I and II of the entire brain stem from the area postrema to C2 level, being maximum at the decussatio pyramidum level. The area postrema, solitary tract, medullary and lateral reticular nuclei were also labelled. The 5-hydroxytryptamine(1B/1D/1F) receptor agonist sumatriptan (0.01, 0.1, 1 and 10 mg/kg), administered intraperitoneally 15 min before capsaicin stimulation (1 nmol), decreased the c-fos response within Sp5C, but not within solitary tract. The novel specific 5-hydroxytryptamine1F agonist LY 344864 (0.1 and 1 mg/kg, i.p.) significantly decreased the c-fos LI within the Sp5C as well. These findings suggest that intracisternally administered capsaicin activates the trigeminovascular system and that the pain neurotransmission can be modulated by 5-hydroxytryptamine(1B/1D/1F) receptors in mice. Thus, the availability of this model in mice, taken together with the possibility of altering the expression of specific genes in this species, may help to investigate further the importance of distinct proteins in the neurotransmission of cephalic pain.     

Onset of effect of 5-HT1B/1D agonists: a model with pharmacokinetic validation

OBJECTIVE: To quantitate onset of effect of all formulations of sumatriptan, and to investigate whether this is related to rate, not extent, of drug absorption. METHODS: From published literature, for 4 formulations of sumatriptan and matching placebos, response rates were modeled using a simple logarithmic equation, with a being a parameter of curve convexity and B, a location parameter (equal to response rate at 2 hours [the standard regulatory parameter]). The average rate of drug absorption (A) was estimated by dividing the maximal drug concentration by the time needed to achieve it (Cmax/Tmax). Least mean square correlation was then performed between the therapeutic gains and therapeutic ratios of curve convexity and rate of drug absorption. RESULTS:-Models closely fitted observed response rates (2 hours or less). Curve convexity correlated with rate of drug absorption. Sumatriptan response rates (0 to 2 hours) for formulations correlated with rate, not extent, of drug absorption. The range of rates of onset of effect among different routes of administration was greater than that for tablets with 4-fold differences in dose size. CONCLUSION: Onset of effect is related to rate of absorption of sumatriptan. There is greater scope for improving onset of effect using an alternative route of administration than by increasing the oral dose.     

Comparative tolerability of oral 5-HT1B/1D agonists

OBJECTIVES: To compare the relative tolerability of 5-HT1B/1D agonists and to investigate the relationships (if any) among systemic exposure, lipophilicity, and clinical tolerability for 5-HT1B/1D agonists. METHODS: Post hoc correlations were sought among the following variables: absolute dose (= administered dose x oral bioavailability), Cmax, LogDpH7.4 (LogD), frequencies of all, neurological and dizziness/somnolence/drowsiness adverse events, adjusted for corresponding placebo-associated frequencies. RESULTS: For effective doses of all drugs with available data, absolute dose-response relationships exist for adverse event frequencies. The overall rank order of the frequency of adverse events was as follows: naratriptan < sumatriptan = rizatriptan < zolmitriptan. With the exception of eletriptan, 5-HT1B/1D agonists exhibit correlations between absolute dose, Cmax (R = 0.97), and LogD (R = 0. 71). For neurological and dizziness/somnolence/drowsiness adverse event frequencies, the overall rank order was sumatriptan < naratriptan < rizatriptan < zolmitriptan. Neither LogD nor absolute dose size predicted adverse event frequencies. CONCLUSIONS: Triptans may be distinguished in terms of their tolerability. Effectiveness, absolute dose size, and lipophilicity are related for the 5-HT1B/1D agonists considered here, except eletriptan. Adverse event frequencies cannot be predicted from in vitro measures of lipophilicity, in vivo estimates of absolute bioavailability, dose size, or any combination of these variables. Since these drugs are all agonists at 5-HT1B/1D receptors in the low nanomolar range, but differ in their tolerability profiles, adverse effects are not likely to be mediated through 5-HT1B/1D receptors. Drugs of this class must be studied individually and on a reasonably large scale in clinical development programs.     

Biochemical and electrophysiological properties of SR 57746A, a new, potent 5-HT1A receptor agonist

Summary— SR 57746A (1-[2-(naphth-2-yl) ethyl]-4-(3-trifluoromethylphenyl)-1, 2, 5, 6 tetra-hydropyridine hydrochloride) binds competitively, and with high affinity (K_i = 2.0 ± 0.7 nM) to 5-HT_1A receptors from rat hippocampus in vitro , but has much less affinity for other 5-HT receptor subtypes (IC₅₀ > 650 nM). SR 57746A produces a concentration-dependent inhibition of forskolin-stimulated adenylate cyclase activity in rat hippocampal homogenates, with a maximal effect identical to that of 8-OH-DPAT, suggesting that SR 57746A behaves as a full agonist in tthis experimental model. SR 57746A potently displaces [³H]8-OH-DPAT binding to rat hippocampal membranes ex vivo , with an ID₅₀ of 11.1 mg/kg po, 30 min after administration, and 2.8 mg/kg po, 2 h after administration. This effect of SR 57746A is long-lasting (at least 24 hours at 10 mg/kg po). SR 57746A does not modify the levels of 5-HT or DA in various brain areas, but decreases the concentrations of 5-HIAA, and increases those of DOPAC, HVA and 3-MT. Following iv administration, SR 57746A (0.095 to 0.25 mg/kg) inhibits the spontaneous firing of dorsal raphe neurones, but does not modify the activity of DA neurones in the substantia nigra or ventral tegmental area. Thus, SR 57746A is a potent, selective and full agonist at 5-HT_1A receptors in vitro and vivo.