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行为学实验中猫的5-羟色胺能中缝背核神经元对5-HT1A激动剂和拮抗剂给药的单单位反应。

Single-unit responses of serotonergic dorsal raphe neurons to 5-HT1A agonist and antagonist drug administration in behaving cats.

作者信息

Fornal C A, Litto W J, Metzler C W, Marrosu F, Tada K, Jacobs B L

机构信息

Department of Psychology, Princeton University, New Jersey.

出版信息

J Pharmacol Exp Ther. 1994 Sep;270(3):1345-58.

PMID:7932189
Abstract

Single-unit activity of serotonergic neurons in the dorsal raphe nucleus was recorded in free-moving cats in response to i.v. administration of 5-hydroxytryptamine (5-HT)1A agonist and antagonist drugs. The 5-HT1A agonist drugs 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), ipsapirone, buspirone and 5-methoxy-N,N-dimethyltryptamine produced a rapid, dose-dependent inhibition of neuronal activity. 8-OH-DPAT (ED50 = 1.5 micrograms/kg) was approximately 45 times more potent than ipsapirone, buspirone or 5-methoxy-N,N-dimethyltryptamine (ED50 range = 6.0-6.8 micrograms/kg) in producing inhibition, and all drugs were more effective when cats were inactive (e.g., drowsiness) than during periods of behavioral arousal (e.g., active waking). Administration of the 5-HT1A autoreceptor antagonist spiperone (0.25 and 1 mg/kg) produced a rapid, dose-dependent increase in the firing rate, suggesting that under physiological conditions serotonergic neurons are controlled by tonic feedback inhibition. This effect was evident during wakefulness (a period of relatively high neuronal activity), but not during sleep (a period of relatively low neuronal activity). Spiperone also blocked the inhibitory action of 8-OH-DPAT in a dose- and time-dependent manner. There was a strong positive correlation between the magnitude of spiperone-induced neuronal activation and blockade of 8-OH-DPAT-induced neuronal suppression. These effects of spiperone cannot be attributed to its dopaminergic D2 or serotonergic 5-HT2 antagonist properties, because administration of haloperidol and ritanserin produced no increase in neuronal activity and did not block the action of 8-OH-DPAT. These results confirm the marked sensitivity of serotonergic dorsal raphe nucleus neurons to selective 5-HT1A agonist compounds in unanesthetized animals and suggest that 5-HT1A somatodendritic autoreceptors exert a tonic inhibitory influence on the firing rate of these neurons during periods of behavioral activation, but not during periods of behavioral quiescence.

摘要

在自由活动的猫身上记录中缝背核中血清素能神经元的单单位活动,以响应静脉注射5-羟色胺(5-HT)1A激动剂和拮抗剂药物。5-HT1A激动剂药物8-羟基-2-(二正丙基氨基)四氢萘(8-OH-DPAT)、伊沙匹隆、丁螺环酮和5-甲氧基-N,N-二甲基色胺产生了快速的、剂量依赖性的神经元活动抑制。8-OH-DPAT(ED50 = 1.5微克/千克)在产生抑制作用方面比伊沙匹隆、丁螺环酮或5-甲氧基-N,N-二甲基色胺(ED50范围 = 6.0 - 6.8微克/千克)强约45倍,并且当猫不活动(例如困倦)时,所有药物都比行为觉醒期(例如活跃清醒)更有效。给予5-HT1A自身受体拮抗剂舒必利(0.25和1毫克/千克)会导致放电率快速、剂量依赖性增加,这表明在生理条件下,血清素能神经元受紧张性反馈抑制控制。这种效应在清醒期间(神经元活动相对较高的时期)明显,但在睡眠期间(神经元活动相对较低的时期)不明显。舒必利还以剂量和时间依赖性方式阻断了8-OH-DPAT的抑制作用。舒必利诱导的神经元激活程度与8-OH-DPAT诱导的神经元抑制阻断之间存在强烈的正相关。舒必利的这些作用不能归因于其多巴胺能D2或血清素能5-HT2拮抗剂特性,因为给予氟哌啶醇和利坦色林不会导致神经元活动增加,也不会阻断8-OH-DPAT的作用。这些结果证实了在未麻醉动物中血清素能中缝背核神经元对选择性5-HT1A激动剂化合物具有显著敏感性,并表明5-HT1A体树突自身受体在行为激活期对这些神经元的放电率施加紧张性抑制影响,但在行为静止期则不然。

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