Kehne J H, Ketteler H J, McCloskey T C, Sullivan C K, Dudley M W, Schmidt C J
Hoechst Marion Roussel, Inc., Cincinnati, OH 45215, USA.
Neuropsychopharmacology. 1996 Aug;15(2):116-24. doi: 10.1016/0893-133X(95)00160-F.
(+/-)3,4-Methylenedioxymethamphetamine (MDMA) releases dopamine and serotonin in vivo and stimulates locomotor activity. Previous work demonstrated that MDMA-stimulated dopamine release could be reduced by the selective 5-HT2A receptor antagonist [R-(+)-a- (2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidinem ethanol] (MDL 100,907). In the present study MDL 100,907 significantly reduced MDMA-stimulated locomotion without affecting basal levels of locomotion. Other agents with 5-HT2A antagonist activity (ritanserin, clozapine, MDL 28,133A, or methiothepin), as well as agents that block 5-HT1A-(propranolol), D2-(haloperidol), or D1 receptors (SCH 23390) also reduced MDMA-stimulated locomotion. Intraventricularly administered 5,7-dihydroxytryptamine decreased regional 5-HT levels and attenuated MDMA-stimulated locomotion. These data support the conclusion that serotonin released onto 5-HT2A receptors contributes to MDMA-stimulated locomotion and suggest that MDMA-stimulated locomotion may be useful as an in vivo behavioral measure of 5-HT2A antagonism. The data also support previous reports of contributions of 5-HT1A, D1 and D2 receptors to MDMA-stimulated locomotion. A preliminary time-course analysis indicating time-dependent contributions of different receptors to MDMA-stimulated locomotion suggests the potential utility of this model for characterizing potential atypical antipsychotic compounds.
（±）3,4-亚甲基二氧甲基苯丙胺（摇头丸）在体内释放多巴胺和5-羟色胺，并刺激运动活性。先前的研究表明，选择性5-HT2A受体拮抗剂[R-（+）-α-（2,3-二甲氧基苯基）-1-[2-（4-氟苯基）乙基]-4-哌啶乙醇]（MDL 100,907）可减少摇头丸刺激的多巴胺释放。在本研究中，MDL 100,907显著降低了摇头丸刺激的运动活性，而不影响基础运动水平。其他具有5-HT2A拮抗剂活性的药物（利坦色林、氯氮平、MDL 28,133A或甲硫哒嗪），以及阻断5-HT1A-（普萘洛尔）、D2-（氟哌啶醇）或D1受体（SCH 23390）的药物也降低了摇头丸刺激的运动活性。脑室内注射5,7-二羟基色胺可降低局部5-羟色胺水平，并减弱摇头丸刺激的运动活性。这些数据支持以下结论：释放到5-HT2A受体上的5-羟色胺有助于摇头丸刺激的运动活性，并表明摇头丸刺激的运动活性可能作为5-HT2A拮抗作用的体内行为指标。数据还支持先前关于5-HT1A、D1和D2受体对摇头丸刺激的运动活性有作用的报道。初步的时程分析表明不同受体对摇头丸刺激的运动活性有时间依赖性作用，提示该模型在表征潜在非典型抗精神病化合物方面的潜在用途。
