CONDITIONED RELEASE OF CORTICOSTERONE BY CONTEXTUAL STIMULI ASSOCIATED WITH COCAINE IS MEDIATED BY CORTICOTROPIN-RELEASING FACTOR

Elevated blood concentrations of corticosterone (CORT), an adrenal ste roid associated with stress responses, is one of the endocrine correla tes of cocaine treatment. Experiment 1 confirmed and extended previous findings that chronic cocaine treatment does not alter corticosteroid responses to cocaine. In Experiment 2, conditioned endocrine effects of cocaine were examined in three groups of rats after 7 consecutive d ays of treatment. Cocaine-induced conditioning was achieved using a si mple contextual design. In group 1 (paired), rats were injected with c ocaine (30 mg/kg), then immediately placed into a locomotor activity c hamber for 30 min. One hour after the rats were returned to their home cages, they received an injection of saline. In group 2 (unpaired), r ats were injected with saline, then immediately placed into a locomoto r activity chamber for 30 min. One hour after the rats were returned t o their home cages, they received an injection of cocaine (30 mg/kg). Rats in group 3 (control) received only saline injections, but otherwi se were treated as animals in the other treatment groups. On the test day (Day 8), all rats were placed immediately into the locomotor appar atus for 30 min prior to collection of a blood sample. Blood CORT conc entrations and locomotor activity in the paired group were significant ly higher than in the unpaired and control groups. However, pretreatme nt of the rats in Experiment 3 with the corticotropin-releasing factor (CRF) antagonist, alpha-helical CRF9.41 (1 mu g, i.c.v.), on the test day, prior to exposure to cocaine-associated contextual cues, attenua ted the subsequent conditioned increase in blood CORT concentrations. These data represent the first demonstration of classical conditioning of a steroid hormone response to stimuli associated with a psychoacti ve drug in rats and suggest that the effect is mediated by endogenous CRF. Because the hypothalamic-pituitary-adrenal (HPA) axis has been im plicated in modulating the actions of cocaine, it is plausible that su ch conditioned increases in CORT release by cocaine-associated cues ma y further predispose an organism to the reinforcing effects of the dru g or enhance the susceptibility to drug-taking behavior. Alternatively , such conditioned effects may be related to the anxiogenic properties of cocaine. Further understanding of the conditioned effects of hormo nes in the development and expression of addictive behaviors may provi de new insights into treatment of drug addiction. (C) 1998 Elsevier Sc ience B.V.