Selective breeding has produced strains of rats with either high (P) or low preference (NP) for ethanol. The major focus with these rats has been the documentation of their ethanol preference difference. However, there have been a few studies indicating that the two rat strains may display altered cognitive function. If such cognitive differences exit, it raise the question of whether or not the cognitive differences are genetically linked with the ethanol preference. Such a linkage would be important in understand the role of cognitive processes in alcohol dependence. A first step in examining this question will be to determine if there are clear and unambiguous differences in cognitive function between the P and NP rats. Thus this project will examine the performance of P and NP rats in three tests of different aspects of cognitive function. Prior to the initiation of these tests of cognitive function, the degree of motivation of the P and NP rats to lever press for initiation of these tests of cognitive function, the degree of motivation of the P and NP rats to level press for food presentation will be assessed under a progressive ratio schedule. Once motivation factors have been normalized, the two strains of rats will be tested under a test of short-term memory (delayed matching-to-position), a test of temporal discrimination (ability to discriminate a 3-second versus 10-second delay) and a test of learning (repeated acquisition of behavioral chains). 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 two 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 there are clear differences in the cognitive function of the P and NP rats, future experiments will attempt to determine if the differences in ethanol preference and the differences in cognitive function are genetically linked. If they are, it will provide additional potential insight into the role that cognitive processes play in alcohol dependence.
| Wenger, Galen R; Schmidt, Cecilia; Davisson, Muriel T (2004) Operant conditioning in the Ts65Dn mouse: learning. Behav Genet 34:105-19 |
