Heyser C J, Schulteis G, Koob G F
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.
Alcohol Clin Exp Res. 1997 Aug;21(5):784-91.
A predominant feature in human alcohol abuse is the reported desire or "craving" to consume ethanol along with frequent episodes of drinking after periods of abstinence. These and other factors may be responsible for relapse to uncontrolled ethanol drinking. When relapse occurs after a period of abstinence, ethanol drinking has been shown to be temporarily increased. Two aspects of drug dependence could contribute to these increases. One may be the development of a need state; the other may involve changes in the perception of the positive reinforcing effects of ethanol when reinforcer access is limited. To investigate this phenomenon further, the present study was conducted to examine in nondependent rats the effect of forced time-off on oral ethanol self-administration in a limited access paradigm (30 min/day). Male Wistar rats were trained to respond for ethanol (10% w/v) or water in a two-lever, free-choice condition using a saccharin fading procedure. After the establishment of stable baseline responding for ethanol, various ethanol deprivation periods (3, 5, 7, 14, or 28 days) were imposed, during which no ethanol was available. Responding for ethanol increased as a function of the duration of the deprivation period when compared with baseline levels. This increase was temporary and returned to baseline levels within 2 to 3 days. Given that the shortest time-off period was 5 days and the rats showed no signs of withdrawal, this transient increase in ethanol responding does not seem to be related to the manifestation of dependence and withdrawal, and may be related to changes in ethanol's reinforcement properties. These results with rats may provide a useful tool to elucidate mechanisms underlying human alcohol seeking behavior and relapse.
人类酒精滥用的一个主要特征是，据报告存在饮用乙醇的欲望或“渴望”，且在禁欲一段时间后会频繁饮酒。这些因素以及其他因素可能是导致复饮至无节制饮酒的原因。在禁欲一段时间后复饮时，乙醇摄入量会暂时增加。药物依赖的两个方面可能导致了这种增加。一方面可能是产生了需求状态；另一方面可能涉及当强化物获取受限，乙醇的正性强化作用的认知发生变化。为了进一步研究这一现象，本研究旨在考察在非依赖大鼠中，限时获取范式（每天30分钟）下强制禁饮对口服乙醇自我给药的影响。雄性Wistar大鼠通过糖精递减程序，在双杠杆自由选择条件下接受训练，以获取乙醇（10% w/v）或水。在建立稳定的乙醇基线反应后，施加不同的乙醇剥夺期（3、5、7、14或28天），在此期间不提供乙醇。与基线水平相比，对乙醇的反应随着剥夺期的延长而增加。这种增加是暂时的，在2至3天内恢复到基线水平。鉴于最短的禁饮期为5天，且大鼠没有出现戒断迹象，乙醇反应的这种短暂增加似乎与依赖和戒断的表现无关，可能与乙醇强化特性的变化有关。这些大鼠实验结果可能为阐明人类酒精寻求行为和复饮的潜在机制提供有用的工具。
