Chester J A, Cunningham C L
Department of Behavioral Neuroscience, and Portland Alcohol Research Center, Oregon Health Sciences University, 97201-3098, USA.
Pharmacol Biochem Behav. 1999 Jun;63(2):325-31. doi: 10.1016/s0091-3057(98)00253-6.
The present experiments examined the effects of the GABA(B) receptor agonist, baclofen, on the acquisition of ethanol-induced conditioned place preference (CPP) and conditioned taste aversion (CTA) in male DBA/2J mice. Mice in the CPP experiment received four pairings of ethanol (2g/kg) with a distinctive floor stimulus for a 5-min conditioning session (CS+ sessions). On intervening days (CS- sessions), mice received saline injections paired with a different floor type. On CS+ days, mice also received one of four doses of baclofen (0.0. 2.5, 5.0, or 7.5 mg/kg) 15 min before an injection of ethanol. For the preference test, all mice received saline injections, and were placed on a half-grid and half-hole floor for a 60-min session. Baclofen dose dependently reduced ethanol-stimulated activity, but did not alter the magnitude of ethanol-induced CPP at any dose. For the CTA experiment, mice were adapted to a 2-h per day water restriction regimen followed by five conditioning trials every 48 h. During conditioning trials, subjects received an injection of saline or baclofen (2.0 and 6.0 mg/kg) 15 min before injection of 2 g/kg ethanol or saline following 1-h access to a saccharin solution. Baclofen did not alter the magnitude of ethanol-induced CTA at any dose. In addition, baclofen alone did not produce a CTA. Overall, these studies show that activation of GABA(B) receptors with baclofen reduces ethanol-induced locomotor activation, but does not alter ethanol's rewarding or aversive effects in the CPP and CTA paradigms in DBA/2J mice.
本实验研究了γ-氨基丁酸B(GABA(B))受体激动剂巴氯芬对雄性DBA/2J小鼠乙醇诱导的条件性位置偏爱(CPP)和条件性味觉厌恶(CTA)形成的影响。在CPP实验中,小鼠在5分钟的条件化训练环节(CS+环节)中接受4次乙醇(2g/kg)与独特地面刺激的配对。在间隔日(CS-环节),小鼠接受与不同地面类型配对的生理盐水注射。在CS+日,小鼠在注射乙醇前15分钟还接受四种剂量(0.0、2.5、5.0或7.5mg/kg)之一的巴氯芬注射。在偏爱测试中,所有小鼠接受生理盐水注射,并被放置在一个半网格半孔洞的地面上60分钟。巴氯芬剂量依赖性地降低了乙醇刺激的活动,但在任何剂量下均未改变乙醇诱导的CPP程度。在CTA实验中,小鼠先适应每天2小时的限水方案,然后每48小时进行5次条件化试验。在条件化试验期间,实验对象在接触糖精溶液1小时后,注射2g/kg乙醇或生理盐水前15分钟接受生理盐水或巴氯芬(2.0和6.0mg/kg)注射。巴氯芬在任何剂量下均未改变乙醇诱导的CTA程度。此外,单独使用巴氯芬不会产生CTA。总体而言,这些研究表明,用巴氯芬激活GABA(B)受体可降低乙醇诱导的运动激活,但在DBA/2J小鼠的CPP和CTA范式中不会改变乙醇的奖赏或厌恶效应。