A number of studies have shown altered cognitive function in humans who abuse ethanol and other drugs of abuse. However, it is not clear whether these differences existed prior to the abuse or whether the differences are the result of the abuse. An initial approach to answering this question is to examine cognitive function in animals with known differences in preference for an abused substance, alcohol. If differences in memory and learning can be demonstrated and shown to be associated with alcohol preference, it would suggest a possible genetic association between altered memory and learning function and alcohol preference. Such a finding could provide insight into the possible role of cognitive differences observed in humans that abuse ethanol. Selective breeding has produced strains of rats with either high (P, HAD1, HAD2) or low preference (NP, LAD1, LAD2) for ethanol. The major research focus with these rats has been the documentation of their ethanol preference difference. However, there have been a few studies indicating that these rat strains may display altered cognitive function. Thus this project will examine the performance of rats with high alcohol preference (P, HAD1, HAD2) and rats with low alcohol preference ( NP, LAD1, LAD2) rats in an operant model of working memory and two models of repeated learning. Prior to the initiation of these tests of cognitive function, the degree of motivation of the rats to lever press for food presentation will be assessed under a progressive ratio schedule. If motivation differences are detected, an attempt to reduce the differences in motivation will be conducted by adjusting body weights. Once motivational factors have been normalized, the working memory and learning performance of the rats will be examined. The performance of the rats will be assessed under control conditions and following doses of ethanol, diazepam, scopolamine and methscopolamine. Ethanol was selected because of its reported effect on short-term memory in humans and laboratory animals and because of the reported differences in preference between the strains. Diazepam was selected because of its known effects on cognitive function and action at the GABA receptor. Scopolamine was selected because it is a prototype amnesic agent believed to act via cholinergic rather than GABA systems. Methscopolamine will be studied to control for peripheral actions of scopolamine. If it can be shown that differences in the cognitive function of the rats is associated with alcohol preference or non-preference, it will provide additional potential insight into the role that cognitive processes play in alcohol dependence, and possibly open new treatment avenues
| Comer, Sandra D; Bickel, Warren K; Yi, Richard et al. (2010) Human behavioral pharmacology, past, present, and future: symposium presented at the 50th annual meeting of the Behavioral Pharmacology Society. Behav Pharmacol 21:251-77 |
| Wenger, Galen R; Hall, Camron J (2010) Rats selectively bred for ethanol preference or nonpreference have altered working memory. J Pharmacol Exp Ther 333:430-6 |
