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丁螺环酮在动物冲突试验中的作用:与地西泮和苯巴比妥的比较。

Buspirone effects in an animal conflict procedure: comparison with diazepam and phenobarbital.

作者信息

McCloskey T C, Paul B K, Commissaris R L

出版信息

Pharmacol Biochem Behav. 1987 May;27(1):171-5. doi: 10.1016/0091-3057(87)90492-8.

DOI:10.1016/0091-3057(87)90492-8
PMID:3615539
Abstract

Buspirone has been introduced as a novel non-benzodiazepine anti-anxiety agent. The Conditioned Suppression of Drinking (CSD) paradigm is an "animal model" for anxiety which provides information on both the relative potency and relative efficacy of anti-conflict agents. The present study compared the anti-conflict effects of buspirone to those of more "classical" anti-anxiety agents, diazepam and phenobarbital. In daily 10-minute sessions, water-deprived rats were trained to drink from a tube which was occasionally electrified (0.5 mA), electrification being signalled by a tone. Within 2-3 weeks control CSD responding had stabilized (approximately 15-20 shocks/session and 10-15 ml water/session); drug tests were conducted at weekly intervals. Diazepam and phenobarbital markedly (400-500%) increased the number of shocks received at doses which did not depress background responding (i.e., water intake). A number of agents, most notably morphine and ethanol, did not reliably affect punished responding in the CSD. Administered IP, low doses (0.25-1 mg/kg) of buspirone increased punished responding only slightly (less than 100% increase); higher doses (2, 4 mg/kg) depressed background responding. Administered SC, buspirone (0.125-1.0 mg/kg) had more potent effects on both punished and unpunished responding; again, anti-conflict efficacy was only marginal. These results suggest that buspirone might be less effective than the benzodiazepines in the management of anxiety.

摘要

丁螺环酮已作为一种新型非苯二氮䓬类抗焦虑药被引入。条件性饮水抑制(CSD)范式是一种用于焦虑的“动物模型”,它能提供有关抗冲突药物相对效力和相对疗效的信息。本研究比较了丁螺环酮与更“经典”的抗焦虑药地西泮和苯巴比妥的抗冲突效果。在每日10分钟的实验环节中,对缺水的大鼠进行训练,使其从一根偶尔会通电(0.5毫安)的管子饮水,通电由一个音调信号表示。在2至3周内,对照CSD反应已稳定(每次实验约15至20次电击和10至15毫升水);药物测试每周进行一次。地西泮和苯巴比妥在不抑制背景反应(即饮水量)的剂量下显著(400 - 500%)增加了接受电击的次数。许多药物,最显著的是吗啡和乙醇,在CSD中对受惩罚反应没有可靠影响。腹腔注射时,低剂量(0.25 - 1毫克/千克)的丁螺环酮仅轻微增加受惩罚反应(增加不到100%);高剂量(2、4毫克/千克)则抑制背景反应。皮下注射时,丁螺环酮(0.125 - 1.0毫克/千克)对受惩罚和未受惩罚反应都有更强的作用;同样,抗冲突疗效仅为边缘性。这些结果表明,在焦虑管理方面,丁螺环酮可能不如苯二氮䓬类药物有效。

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