ACQUISITION AND MAINTENANCE OF INTRAVENOUS COCAINE SELF-ADMINISTRATION IN LEWIS AND FISCHER INBRED RAT STRAINS

Lewis and Fischer inbred rat strains differ in behavioral and biochemi cal responses to psychoactive drugs: Lewis rats show greater behaviora l responses to psychoactive drugs than Fischer rats and they fail to s how biochemical adaptations in the mesolimbic dopamine system after ch ronic drug exposure, in contrast to Fischer and outbred rats. This sug gests that Fischer and Lewis rats may differ in the initial, reinforci ng effects of psychoactive drugs, but not in responses seen after the exposure that occurs with maintenance of drug-reinforced behavior. Thu s, the present study tested whether these strains differ in acquisitio n or maintenance of intravenous cocaine self-administration. Acquisiti on of cocaine self-administration was examined in separate groups that were allowed 15 days to acquire the operant at one of three cocaine d oses (0.25, 0.5, or 1.0 mg/kg/infusion). Compared to Fischer rats, Leu is rats acquired cocaine self-administration after fewer training tri als and at lower doses. After maintenance, both strains showed charact eristic extinction responding with saline substitution and dose-relate d responding to cocaine, although Fischer rats tended to show higher r esponse rates. Finally, cocaine plasma levels, obtained after an intra venous cocaine infusion (1.0 mg/kg), showed no strain differences sugg esting that the strain difference in acquisition was not due to cocain e pharmacokinetics. These strain differences in acquisition of cocaine self-administration may be related to reported strain differences in the mesolimbic dopamine system. Further, because acquisition of drug s elf-administration is an animal model of vulnerability to drug addicti on, these inbred strains may be useful to study factors underlying suc h vulnerability. (C) 1997 Elsevier Science B.V.