Rodd-Henricks Zachary A, Bell Richard L, Kuc Kelly A, Murphy James M, McBride William J, Lumeng Lawrence, Li Ting-Kai
Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis 46202-4887, USA.
Alcohol Clin Exp Res. 2002 Nov;26(11):1642-52. doi: 10.1097/01.ALC.0000036302.73712.9D.
In a preceding study, we reported that ethanol (EtOH) consumption during periadolescence in alcohol-preferring (P) rats produced significant effects on the acquisition, extinction, Pavlovian spontaneous recovery (PSR), and reacquisition of operant self-administration of EtOH. The objective of the present study was to determine if EtOH consumption during adulthood produced similar effects on subsequent operant behaviors.
Adult female P rats (>135 days of age) were given 24 hr free-choice access to 15% EtOH for 30 days or were similarly housed and received water only. After a 15 day period of no EtOH access and without any prior training, adult alcohol drinking and adult alcohol-naïve rats were placed in standard two-lever (15% EtOH and water) chambers to examine acquisition of EtOH self-administration. After stable responding was established on a concurrent fixed ratio (FR) 5 FR1 schedule for EtOH versus water, the P rats underwent extinction training for nine sessions. After extinction and a 2 week home cage period (with no operant sessions or access to EtOH), rats were returned to the operant chambers in the absence of reward for seven consecutive sessions to test for PSR. After PSR testing, animals were maintained in their home cage for a week, before being reintroduced to the operant chambers and allowed to respond for EtOH and water.
Both the adult alcohol-drinking and adult alcohol-naïve groups rapidly acquired EtOH self-administration, expressed a pronounced PSR, which was augmented by EtOH priming and the presence of a discriminative stimulus (odor cue), and increased responding when EtOH was reinstated. Adult pre-exposure to EtOH did not alter any of the operant measures.
The results of this study suggest that, unlike the results with EtOH pre-exposure during periadolescence, chronic alcohol drinking by P rats in adulthood did not produce sufficient long-lasting changes in neuronal function to alter subsequent operant acquisition of alcohol self-administration, alcohol relapse, or alcohol-seeking behavior.
在之前的一项研究中,我们报告称,在酒精偏好(P)大鼠的青春期前后摄入乙醇(EtOH),会对EtOH操作性自我给药的习得、消退、巴甫洛夫式自发恢复(PSR)和重新习得产生显著影响。本研究的目的是确定成年期摄入EtOH是否会对随后的操作性行为产生类似影响。
成年雌性P大鼠(>135日龄)可自由选择饮用15%的EtOH 24小时,持续30天,或同样饲养但只给予水。在15天不接触EtOH且没有任何先前训练的时期后,成年饮酒大鼠和成年未接触过酒精的大鼠被置于标准的双杠杆(15% EtOH和水)实验箱中,以检查EtOH自我给药的习得情况。在建立了EtOH与水的并行固定比率(FR)5 FR1时间表的稳定反应后,P大鼠接受了9次消退训练。在消退训练和2周的饲养笼期(没有操作性实验或接触EtOH)后,大鼠在没有奖励的情况下连续7次返回操作性实验箱以测试PSR。在PSR测试后,动物在饲养笼中饲养一周,然后重新引入操作性实验箱,并允许它们对EtOH和水做出反应。
成年饮酒组和成年未接触过酒精的组都迅速习得EtOH自我给药,表现出明显的PSR,EtOH启动和辨别性刺激(气味线索)的存在增强了这种反应,并且在重新引入EtOH时反应增加。成年期预先接触EtOH并没有改变任何操作性测量结果。
本研究结果表明,与青春期前后预先接触EtOH的结果不同,成年期P大鼠长期饮酒并未在神经元功能上产生足够持久的变化,以改变随后酒精自我给药的操作性习得、酒精复发或觅酒行为。