Interaction of Extinguished Cocaine-Conditioned Stimuli and Footshock on Reinstatement in Rats

The reinstatement paradigm has been proposed as an animal model of human drug relapse. In most reinstatement studies, conditioned stimuli accompany drug infusions during self-administration, responding in extinction, as well as responding during reinstatement tests. The importance of these extinguished drug-paired stimuli during stress-induced reinstatement has not been examined. In this study, rats were trained to self-administer 0.5 mg/kg/infusion cocaine during daily, 2-h sessions until behavior stabilized. Each cocaine infusion was accompanied by a 6-s flashing light + tone conditioned stimulus (CS). In two groups of rats, responding during subsequent extinction and reinstatement had no scheduled consequences (CS Omitted). In two other groups of rats, responding produced the light + tone but no cocaine injections (CS Present). Footshock did not significantly reinstate cocaine seeking behavior in CS Omitted rats. Footshock significantly reinstated cocaine-seeking behavior over multiple test sessions in both CS Present groups, regardless of whether footshock reinstatement was examined on consecutive days or with trials spaced two days apart. These data show that environmental stimuli and stressors which are ineffective by themselves to occasion reinstatement of cocaine-seeking behavior can do so if concurrently present