Different patterns of pharmacological reinstatement of cocaine-seeking behavior between Fischer 344 and Lewis rats

Rationale Fischer 344 (F344) and Lewis (LEW) rats differ in cocaine self-administration behaviors. Whether or not these inbred strains of rats differ in pharmacological reinstatement of cocaine-seeking behavior is unknown.Objectives The purpose of the present study was to determine if inbred strains of rats demonstrate differences in alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) and cocaine-induced reinstatement of previously extinguished cocaine-seeking behavior.Methods F344 and LEW rats received indwelling jugular catheters, bilateral guide cannula aimed at the nucleus accumbens core, and were trained to lever press for 0.5 mg/kg intravenous cocaine during 2-h self-administration sessions. Following 14 sessions, rats underwent extinction sessions, where previously reinforced lever pressing resulted in no programmed consequences. Just prior to beginning extinction session 7, rats received an intracranial infusion of saline. Lever pressing was not reinforced. During subsequent extinction sessions, rats received AMPA injections (0.2, 0.4, or 0.6 nM). Dosing order was determined by a within-subject Latin square design. At least two extinction sessions separated each AMPA session. Rats then underwent cocaine-induced reinstatement test sessions (lever pressing was not reinforced). Rats received passive intravenous cocaine (0.0, 0.5, 1.0, or 2.0 mg/kg) after being placed in the experimental chamber. At least two extinction sessions separated each cocaine-prime session, and subjects were tested at each dose according to a within-subjects Latin square design.Results LEW rats demonstrated blunted maximal responding to AMPA-induced reinstatement and heightened sensitivity to cocaine-induced reinstatement compared with F344 rats.Conclusions This study demonstrates that inbred strains differ in pharmacological reinstatement of cocaine-seeking behavior.