Rats bred for differences in preference to cocaine: other behavioral measurements.

Cocaine has repeatedly been shown to produce conditioned place preference (CPP) in the rat. The present study employed the heterogenous N/Nih rat stock to produce a selectively bred rat line determined by individual place preference to a conditioning dose of 2.5 mg/kg cocaine. As each of three generations of rats were exposed to the CPP task, cocaine-preferring (CP) males were mated with CP females whereas cocaine-nonpreferring (CNP) male rats were paired with their female counterparts. Rats in litters of the third generation of these selectively bred rats were used in two collateral studies: one involving the discriminative stimulus properties of cocaine and the other to investigate the ability of cocaine to stimulate activity. Results indicate that the continued breeding of CP animals has resulted in rats that prefer cocaine, whereas the breeding of CNP rats is defining a line of rats that actually find cocaine aversive. In testing the discriminative stimulus performance of five male CP and five male CNP rats, the learning rates and dose-response relationship to cocaine were not significantly different between these two groups. In contrast, administration of 5.0 and 7.5 mg/kg cocaine to male and female CP and CNP rats indicated that, although all groups were stimulated by cocaine when compared to vehicle administration, male CNP rats showed a significantly decreased reaction to these two doses of cocaine. The possibility that conditioned place preference and locomotor stimulation are subserved by the same neural substrates, that is, most probably the dopaminergic systems in the nucleus accumbens of the brain, is discussed.