Differential involvement of GABAA and GABAB receptors in propofol self-administration in rats  

作　　者：Bo YANG Ben-fu WANG Miao-jun LAI Fu-qiang ZHANG Xiao-wei YANG Wen-hua ZHOU Qing-quan LIAN 

机构地区：[1]Department of Anesthesiology of the 2nd Affiliated Hospital and Institute of Neuroendocrinology, Wenzhou Medical College, Wenzhou 325000, China [2]Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo 315010, China

出　　处：《Acta Pharmacologica Sinica》2011年第12期1460-1465,共6页中国药理学报（英文版）

摘　　要：Aim： Propofol has shown abuse potential. The aim of the present study is to investigate the effects of GABAA antagonist and GABAB agonist on propofol reinforcement. Methods： Sprague-Dawley rats were trained to self-administer propofol at a dose of 1.7 mg/kg per infusion under a fixed ratio （FR1） schedule of reinforcement for 14 d. In a separate set of experiments, food-maintained self-administration under a fixed ratio （FR5） schedule and locomotor activities of Sprague-Dawley rats were examined. Results： GABAA receptor antagonist bicuculline （0.25 mg/kg, ip） significantly increased the number of injections and active responses. Pretreatment with GABAB receptor agonist baclofen （3 mg/kg, ip） significantly decreased the number of active responses and total infusions of propofol during the training session. Moreover, microinjection of baclofen （50 and 100 ng/side） into the ventral tegmental area （VTA） significantly decreased the number of active responses and total infusions of propofol. Neither baclofen （1-3 mg/kg, ip） nor bicuculline （0.25-1 mg/kg, ip） affected food-maintained responses or motor activities. Conclusion： Propofol maintains its reward properties partially through GABAA receptor activation. Stimulation of GABAB receptors in VTA may counteract the reinforcing properties of propofol.Aim： Propofol has shown abuse potential. The aim of the present study is to investigate the effects of GABAA antagonist and GABAB agonist on propofol reinforcement. Methods： Sprague-Dawley rats were trained to self-administer propofol at a dose of 1.7 mg/kg per infusion under a fixed ratio （FR1） schedule of reinforcement for 14 d. In a separate set of experiments, food-maintained self-administration under a fixed ratio （FR5） schedule and locomotor activities of Sprague-Dawley rats were examined. Results： GABAA receptor antagonist bicuculline （0.25 mg/kg, ip） significantly increased the number of injections and active responses. Pretreatment with GABAB receptor agonist baclofen （3 mg/kg, ip） significantly decreased the number of active responses and total infusions of propofol during the training session. Moreover, microinjection of baclofen （50 and 100 ng/side） into the ventral tegmental area （VTA） significantly decreased the number of active responses and total infusions of propofol. Neither baclofen （1-3 mg/kg, ip） nor bicuculline （0.25-1 mg/kg, ip） affected food-maintained responses or motor activities. Conclusion： Propofol maintains its reward properties partially through GABAA receptor activation. Stimulation of GABAB receptors in VTA may counteract the reinforcing properties of propofol.

关 键 词：addiction PROPOFOL drug abuse. GABA receptors BACLOFEN BICUCULLINE ventral tegmental area （VTA） locomotor activity 

分 类 号：Q424[生物学—神经生物学] TQ460.72[生物学—生理学]