Saydoff J A, Rittenhouse P A, van de Kar L D, Brownfield M S
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison.
J Pharmacol Exp Ther. 1991 Apr;257(1):95-9.
The involvement of serotonin (5-HT) in oxytocin secretion was investigated in this study. Pharmacologic agents that influence serotonergic transmission were administered to conscious unrestrained male rats 30 min prior to sacrifice and plasma oxytocin concentration was measured by radioimmunoassay. The d- and l-stereoisomers of the 5-HT releaser fenfluramine significantly increased plasma oxytocin in a dose-dependent manner. Oxytocin secretion was more potently stimulated by d-fenfluramine than by l-fenfluramine. The 5-HT releaser p-chloroamphetamine also increased plasma oxytocin. The following 5-HT agonists increased plasma oxytocin concentration: the 5-HT1&2 agonist m-chlorophenyl-piperazine [10-20 mg/kg intraperitoneally (i.p.)], the 5-HT1C&2 agonist 1-(2,5-dimethoxy-4-l-phenyl)-2-aminopropane (0.5-2.0 mg/kg i.p.) and the 5-HT1&2 agonist 1-piperazinyl-6-chloropyrazine (10 mg/kg i.p.). In contrast, the 5-HT1AB agonist 5-methoxy-3-(1,2,3,4-tetrahydro-4-pyridinyl)-1H-indole (0.2-5.0 mg/kg i.p.) did not increase oxytocin secretion. Pretreatment with the 5-HT1C&2 antagonist, 6-(2-(4-[bis(4-fluorophenyl)methylene]-1-piperidinyl)ethyl)-7-methyl-5H- thiazolo(3(1)2-a)pyrimidin-5-one [2.5 mg/kg subcutaneously (s.c.)], 60 min before injection of 1-piperazinyl-6-chloropyrazine attenuated, but did not completely block, 1-piperazinyl-6-chloropyrazine-induced secretion of oxytocin. Both low and high (0.01 and 0.1 mg/kg s.c.) doses of 6-(2-(4-[bis(4-fluorophenyl)methylene]-1-piperidinyl)ethyl)-7-methyl-5H- thiazolo(3(1)2-a)pyrimidin-5-one or the 5-HT2 antagonist spiperone inhibited the 1-(2,5-dimethoxy-4-l-phenyl)-2-aminopropane-induced increases in plasma oxytocin. These studies provide evidence that enhanced serotonergic transmission stimulates oxytocin secretion and that 5-HT2 receptors contribute to this effect.
本研究调查了血清素（5-羟色胺，5-HT）在催产素分泌中的作用。在处死前30分钟，给清醒自由活动的雄性大鼠施用影响血清素能传递的药物，并通过放射免疫测定法测量血浆催产素浓度。5-HT释放剂芬氟拉明的d-和l-立体异构体以剂量依赖性方式显著增加血浆催产素。d-芬氟拉明比l-芬氟拉明更有效地刺激催产素分泌。5-HT释放剂对氯苯丙胺也增加血浆催产素。以下5-HT激动剂增加血浆催产素浓度：5-HT1&2激动剂间氯苯哌嗪[10-20毫克/千克腹腔注射（i.p.）]、5-HT1C&2激动剂1-(2,5-二甲氧基-4-l-苯基)-2-氨基丙烷（0.5-2.0毫克/千克i.p.）和5-HT1&2激动剂1-哌嗪基-6-氯吡嗪（10毫克/千克i.p.）。相比之下，5-HT1AB激动剂5-甲氧基-3-(1,2,3,4-四氢-4-吡啶基)-1H-吲哚（0.2-5.0毫克/千克i.p.）并未增加催产素分泌。在注射1-哌嗪基-6-氯吡嗪前60分钟，用5-HT1C&2拮抗剂6-(2-(4-[双(4-氟苯基)亚甲基]-1-哌啶基)乙基)-7-甲基-5H-噻唑并(3(1)2-a)嘧啶-5-酮[2.5毫克/千克皮下注射（s.c.）]预处理可减弱但未完全阻断1-哌嗪基-6-氯吡嗪诱导的催产素分泌。低剂量和高剂量（0.01和0.1毫克/千克s.c.）的6-(2-(4-[双(4-氟苯基)亚甲基]-1-哌啶基)乙基)-7-甲基-5H-噻唑并(3(1)2-a)嘧啶-5-酮或5-HT2拮抗剂螺哌隆均抑制1-(2,5-二甲氧基-4-l-苯基)-2-氨基丙烷诱导的血浆催产素增加。这些研究提供了证据，表明增强的血清素能传递刺激催产素分泌，且5-HT2受体促成了这一效应。
