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致焦虑药物育亨宾在雄性和雌性大鼠中是一种强化物。

The anxiogenic drug yohimbine is a reinforcer in male and female rats.

作者信息

Renda Briana, Leri Francesco

机构信息

Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, ON, Canada.

Department of Psychology, University of Toronto, Scarborough, ON, Canada.

出版信息

Neuropsychopharmacology. 2024 Dec;50(2):432-443. doi: 10.1038/s41386-024-01985-1. Epub 2024 Sep 17.

Abstract

The indole alkaloid yohimbine is an anxiogenic drug that activates stress-responsive systems in the brain. However, because yohimbine also elicits approach behaviors, this study employed male and female Sprague-Dawley rats to explore its potential reinforcing effects. Thus, it was first determined if intravenous (IV) infusions of yohimbine (0.25 mg/kg/infusion) could maintain lever pressing, whether intake could be modulated by dose/infusion, and if lever pressing would persist in the absence of yohimbine or yohimbine-paired cues. Next, to assess yohimbine's effect on memory consolidation, 0.3, 1.25 or 3 mg/kg yohimbine was administered post-training using an object recognition memory task. Finally, place conditioning assessed whether doses of yohimbine that elevate blood serum corticosterone levels (1.25 or 3 mg/kg) could elicit a conditioned place preference. It was found that both sexes acquired yohimbine IV self-administration, that intake was modulated by dose/infusion, and that lever pressing persisted during extinction and in the absence of the yohimbine-paired cue. As well, post-training injections of 1.25 mg/kg yohimbine enhanced consolidation of object memory, and 1.25 and 3 mg/kg elevated corticosterone levels and elicited a place preference in both sexes. Finally, in behavioral tests of psychomotor functions, acute yohimbine increased lever pressing for a visual cue and elevated locomotor activity. These findings reveal a profile of yohimbine's behavioral effects that is consistent with that of psychostimulant reinforcing drugs.

摘要

吲哚生物碱育亨宾是一种能激活大脑应激反应系统的致焦虑药物。然而,由于育亨宾也会引发趋近行为,本研究采用雄性和雌性斯普拉格-道利大鼠来探究其潜在的强化作用。因此,首先确定静脉注射(IV)育亨宾(0.25毫克/千克/次注射)是否能维持杠杆按压行为,摄入量是否能通过剂量/注射量进行调节,以及在没有育亨宾或与育亨宾配对的线索时杠杆按压行为是否会持续。接下来,为了评估育亨宾对记忆巩固的影响,在训练后使用物体识别记忆任务给予0.3、1.25或3毫克/千克的育亨宾。最后,通过条件性位置偏爱实验评估能升高血清皮质酮水平的育亨宾剂量(1.25或3毫克/千克)是否能引发条件性位置偏爱。研究发现,两性均习得静脉注射育亨宾的自我给药行为,摄入量受剂量/注射量调节,并且在消退期以及没有与育亨宾配对的线索时杠杆按压行为仍持续。此外,训练后注射1.25毫克/千克的育亨宾增强了物体记忆的巩固,1.25和3毫克/千克的剂量升高了皮质酮水平并在两性中均引发了位置偏爱。最后,在精神运动功能的行为测试中,急性给予育亨宾增加了对视觉线索的杠杆按压行为并提高了运动活性。这些发现揭示了育亨宾的行为效应特征,与精神兴奋剂类强化药物的效应特征一致。

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