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成年嗜酒(P)大鼠乙醇暴露对随后乙醇自我给药的习得与消退及觅酒行为表达的影响:I. 青春期前后暴露

Effects of ethanol exposure on subsequent acquisition and extinction of ethanol self-administration and expression of alcohol-seeking behavior in adult alcohol-preferring (P) rats: I. Periadolescent exposure.

作者信息

Rodd-Henricks Zachary A, Bell Richard L, Kuc Kelly A, Murphy James M, McBride William J, Lumeng Lawrence, Li Ting-Kai

机构信息

Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis 46202-4887, USA.

出版信息

Alcohol Clin Exp Res. 2002 Nov;26(11):1632-41. doi: 10.1097/01.ALC.0000036301.36192.BC.

Abstract

BACKGROUND

The current study examined the effects of ethanol (EtOH) drinking during periadolescence on the subsequent acquisition and extinction of operant self-administration of EtOH and expression of alcohol-seeking behavior in adult alcohol-preferring (P) rats to test the hypothesis that alcohol drinking during periadolescence produces enduring alterations that enhance the reinforcing properties of EtOH.

METHODS

Periadolescent female P rats were given 24 hr free-choice access to 15% (v/v) EtOH starting at postnatal day (PND) 30 and ending on PND 60 or were similarly housed and received water only. On PND 75, without any prior training, periadolescent alcohol-drinking and periadolescent alcohol-naïve rats were placed in standard two-lever (15% EtOH and water) chambers to examine acquisition of EtOH self-administration with a fixed ratio (FR) 1 schedule of reinforcement. After the acquisition phase and after stable responding was established on an FR5 for EtOH and FR1 for water, P rats underwent extinction training for both EtOH and water rewards. After extinction training and a 2 week home cage period, rats were returned to the operant chambers in the absence of reward for seven consecutive sessions (Pavlovian spontaneous recovery). After this testing period, animals were maintained in their home cage for a week before being returned to the operant chambers and allowed to respond for EtOH and water (reacquisition).

RESULTS

Compared with periadolescent alcohol-naïve rats, periadolescent alcohol-drinking rats acquired EtOH responding sooner (i.e., in the first acquisition session), displayed a greater resistance to extinguish EtOH responding (i.e., higher levels of responding in sessions 4-6), had higher responding for more sessions on the EtOH lever in the absence of reward after a prolonged home cage rest period, and had a more prolonged elevated level of EtOH responding during reacquisition (four sessions versus one session).

CONCLUSIONS

Overall, the results suggest that periadolescent EtOH drinking by P rats produced long-lasting alterations in the reinforcing effects of alcohol, which increased the likelihood that alcohol drinking would be initiated in adulthood, decreased the likelihood that once adult alcohol drinking began it could be extinguished easily, and increased the potential for relapse.

摘要

背景

本研究考察了青春期前后饮酒对成年偏爱酒精(P)大鼠随后操作性自我给药获取和消退乙醇以及觅酒行为表达的影响,以检验青春期前后饮酒会产生持久改变从而增强乙醇强化特性这一假设。

方法

青春期前后的雌性P大鼠从出生后第30天(PND)开始,有24小时自由选择饮用15%(v/v)乙醇的机会,持续到PND 60,或者同样饲养但只给予水。在PND 75时,未经任何预先训练,将青春期前后饮酒和青春期前后未饮酒的大鼠置于标准双杠杆(15%乙醇和水)实验箱中,以固定比率(FR)1强化程序检验乙醇自我给药的获取情况。在获取阶段之后,当乙醇的FR5和水的FR1建立起稳定反应后,P大鼠接受乙醇和水奖励的消退训练。在消退训练和2周笼内饲养期之后,大鼠在无奖励情况下连续七次返回操作性实验箱(巴甫洛夫式自发恢复)。在此测试期之后,动物在笼内饲养一周,然后再返回操作性实验箱并允许对乙醇和水做出反应(重新获取)。

结果

与青春期前后未饮酒的大鼠相比,青春期前后饮酒的大鼠更快获取了对乙醇的反应(即在第一次获取实验中),对乙醇反应的消退表现出更大的抵抗力(即第4 - 6次实验中反应水平更高),在长时间笼内休息期后无奖励情况下,在乙醇杠杆上有更多实验次数的更高反应水平,并且在重新获取期间乙醇反应水平升高的持续时间更长(四次实验对一次实验)。

结论

总体而言,结果表明青春期前后P大鼠饮用乙醇对酒精的强化作用产生了持久改变,这增加了成年期开始饮酒的可能性,降低了成年期一旦开始饮酒就容易戒掉的可能性,并增加了复发的可能性。

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