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


OBJECTIVE
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Erb
Suzanne
S
Centre for the Neurobiology of Stress, Department of Life Science, University of Toronto at Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada. erb@utsc.utoronto.ca
Petrovic
Ana
A
Yi
Daniel
D
Kayyali
Hanan
H
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D003042:Cocaine / Q000008:administration & dosage*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D012008:Recurrence; D012646:Self Administration; D013997:Time Factors
D003346:Corticotropin-Releasing Hormone; D003042:Cocaine