Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
J Pharmacol Exp Ther. 2010 May;333(2):430-6. doi: 10.1124/jpet.109.159350. Epub 2010 Feb 22.
To examine whether the cognitive deficit observed in chronic alcoholics is because of the chronic exposure to alcohol or to a factor that contributes to the chronic alcohol use, working memory was evaluated under a delayed matching-to-position task in rats selectively bred for ethanol preference or nonpreference (iP/iNP, iHAD1/iLAD1, and iHAD2/iLAD2). Before the study on working memory, rats were studied under a progressive ratio schedule of food presentation to determine whether differences in motivation to respond for food existed between the alcohol-preferring and -nonpreferring strains. No such differences were observed. Under the delayed matching-to-position schedule, the length of the delay was titrated such that accuracy was maintained at approximately 80%, and the mean length of the delay for each experimental session provided a measure of working memory function. In two (iP/iNP and iHAD1/iLAD1) of the three pairs of selectively bred rats, nonpreference to ethanol was associated with better working memory performance. In the third pair of selectively bred rats (iHAD2/iLAD2), the relationship was reversed, with increased ethanol preference associated with better working memory function after saline administration. After ethanol administration, both the mean delay and the rate of responding were decreased in all six strains. Based upon an ED50 analysis, there was little evidence of strain difference in sensitivity to ethanol on either parameter. Additional studies are needed to better understand the relationship between working memory and ethanol preference in these rats.
为了探究慢性酗酒者的认知缺陷是由于长期暴露于酒精还是由于促成慢性酒精使用的因素,我们在对乙醇偏好或非偏好(iP/iNP、iHAD1/iLAD1 和 iHAD2/iLAD2)的大鼠中进行了延迟匹配位置任务,以评估工作记忆。在研究工作记忆之前,我们在递增比率食物呈现方案下研究了大鼠,以确定在对酒精的偏好和非偏好品系之间是否存在对食物反应的动机差异。没有观察到这种差异。在延迟匹配位置方案下,滴定延迟的长度,以使准确性保持在大约 80%,并且每个实验会话的平均延迟长度提供了工作记忆功能的度量。在三个选择性繁殖大鼠对中的两个(iP/iNP 和 iHAD1/iLAD1)中,对乙醇的非偏好与更好的工作记忆表现相关。在第三个选择性繁殖大鼠对(iHAD2/iLAD2)中,关系发生了逆转,在给予盐水后,增加的乙醇偏好与更好的工作记忆功能相关。在给予乙醇后,所有六个品系的平均延迟和反应率都降低了。基于 ED50 分析,在这两个参数上,对乙醇的敏感性在品系之间几乎没有差异。需要进一步的研究来更好地理解这些大鼠中工作记忆和乙醇偏好之间的关系。