Allopregnanolone influences the consummatory processes that govern ethanol drinking in C57BL/6J mice
Allopregnanolone influences the consummatory processes that govern ethanol drinking in C57BL/6J mice
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DOI：
10.1016/j.bbr.2007.02.028
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发表时间：
2007-05-16
影响因子：
2.7
通讯作者：
Finn, Deborah A.
中科院分区：
文献类型：
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作者：
Ford, Matthew M.;Mark, Gregory P.;Finn, Deborah A.
尽管已有研究表明，全身性别孕酮(Allo；一种GABA(A)受体的正向调节剂)可以增强酒精强化的反应，并调节啮齿动物的饮酒模式，但中央给药Allo对乙醇摄入量的影响尚不清楚。目前的工作是通过一种旨在评估Allo对食欲和消耗过程的影响的程序，检验了颅内Allo对食物和水饱足小鼠体内可操作乙醇自我给药的影响。对雄性C57BL/6J(136)小鼠进行训练，通过连续接触10%乙醇溶液30分钟来加强按压适合酒精的杠杆。在外科植入针对侧脑室的导向导管并随后习惯性地进行车辆输液后，在疗程开始前立即给予Allo(50-400 ng；icv)。进一步评估100和400 ng的Allo剂量对活动室内运动行为的影响。Allo选择性地调节与自我给药的开始和维持相关的乙醇摄入模式，同时保持食欲(即寻求酒精)的措施不变。Allo对饮酒模式的影响与运动行为的变化是分离的，这一点从Allo对反应频率和水平行走距离的影响中得到了证明。这些发现支持这样一个前提，即大脑等位基因水平的操纵可能会影响控制乙醇消费的调节过程。(C)2007 Elsevier B.V.保留所有权利。
Although systemic allopregnanolone (ALLO; a positive modulator of GABA(A) receptors) has been shown to enhance ethanol-reinforced responding and to modulate drinking patterns in rodents, the effects of centrally administered ALLO on ethanol intake are not known. The current work examined the effects of intracranial ALLO on operant ethanol self-administration in food- and water-satiated mice, with a procedure designed to estimate ALLO's influence on appetitive versus consummatory processes. Male C57BL/6J (136) mice were trained to press an ethanol-appropriate lever by being reinforced with 30-min of continuous access to a 10% ethanol solution. Following surgical implantation of a guide cannula aimed at the lateral ventricle and subsequent habituation to vehicle infusions, ALLO (50-400 ng; ICV) was delivered immediately prior to session start. ALLO doses of 100 and 400 ng were further evaluated for their effects on locomotor behavior within activity chambers. ALLO selectively modulated ethanol intake patterns associated With the onset and maintenance of self-administration, while leaving appetitive (i.e., ethanol seeking) measures unaltered. The effects of ALLO on drinking patterns were dissociable from changes in locomotor behavior, as evidenced by the absence of ALLO's influence on response frequency and horizontal distance traveled. These findings support the premise that manipulations in brain ALLO levels may influence the regulatory processes governing ethanol consumption. (c) 2007 Elsevier B.V. All rights reserved.