The effects of cocaine preexposure on cocaine-induced taste aversion learning in Fischer and Lewis rat strains.

The Fischer (F344) and Lewis (LEW) inbred rat strains differ on a number of behaviors, including those induced by a variety of drugs of abuse. Although a number of physiological and biochemical differences between the strains have been reported following both single and repeated drug administration, studies assessing changes in the affective properties of drugs after repeated exposure are limited. To that end, using the F344 and LEW strains, the present study examined the effects of repeated exposure to cocaine on the subsequent acquisition of cocaine-induced conditioned taste aversions, a preparation often used in assessing the development of tolerance to the drug's aversive effects. Specifically, separate groups of male F344 and LEW rats received five injections of 32 mg/kg cocaine (or vehicle) prior to taste aversion conditioning with 32 mg/kg cocaine (or vehicle). Vehicle-preexposed subjects of both strains acquired aversions to the cocaine-associated taste with no differences in the strength of the aversions. Further, cocaine-preexposed subjects displayed significantly attenuated aversions, an effect consistent with prior work with outbred animals. There was no difference between the two strains in this attenuation, suggesting that there were no genotype-specific differences in tolerance to cocaine's aversive effects. The data were discussed in relation to genetic/environmental interactions in the vulnerability to drugs of abuse.