Central injections of CRF reinstate cocaine seeking in rats after postinjection delays of up to 3 h: an influence of time and environmental context

Abstract

In drug addicts, the induction of drug craving is not always associated with an immediate opportunity to take drugs again. It is, therefore, important to study how delays in opportunity for drug seeking affect the time-course of relapse. Intracerebroventricular (i.c.v.) injection of corticotropin-releasing factor (CRF) is a stressor that reinstates heroin and alcohol seeking in rats, when administered just before tests for reinstatement. It is not known whether CRF reinstates cocaine seeking; moreover, the effect of delaying testing for reinstatement, after CRF injection, has not been studied. To determine whether i.c.v. CRF induces reinstatement of cocaine seeking after postinjection delays of up to 3 h and to determine whether the context in which a delay is experienced influences the time-course of CRF-induced reinstatement. Rats self-administered cocaine (1.0 mg/kg per infusion) for 8-10 days. Subsequently, responding for drug was extinguished and testing for reinstatement by i.c.v. CRF (0.5 microg) was conducted. Animals were tested after postinjection delays of up to 3 h; the delays were experienced either in the self-administration (SA) chamber or home cage (HC). When delays were spent in the SA chambers, CRF induced reinstatement in all delay groups. When delays were spent in the HC, CRF did not induce reinstatement after a 2-h delay. We argue that the effects we observed are consistent with a contextual conditioning account of reinstatement, whereby CRF that was experienced in the context of the SA chamber served to elicit a conditioned excitatory response developed to that context during training.