The role of corticotrophin-releasing factor in stress-induced relapse to alcohol-seeking behavior in rats

摘要: Rationale: Intermittent footshock stress reliably reinstates extinguished alcohol-taking behavior in drug-free rats, but the neurochemical events involved this effect are not known. Objective: We studied here whether two main modulators of responses, corticotropin-releasing factor (CRF) and corticosterone, reinstatement alcohol seeking induced by intermittent stressor. Methods: Rats were given a two-bottle choice procedure (water versus alcohol) for 30 days then trained 60 min per day to press lever (12% w/v) 24–30 operant conditioning chambers. After stable drug-taking was obtained, pressing terminating drug delivery 5–8 days. Reinstatement determined after exposure (0.8 mA; 10 min) different groups rats that pretreated with CRF receptor antagonists or underwent adrenalectomy (ADX) remove endogenous corticosterone from body. Results: The antagonists, d-phe-CRF (0.3 1.0 µg; ICV) CP-154,526 (15, 45 mg/kg; IP) attenuated footshock-induced dose dependent manner. In contrast, removal circulating ADX had no on stress-induced behavior. addition, prevention rise while maintaining basal levels hormone providing adrenalectomized pellets (50 mg/kg day), reinstatement. Conclusions: These data suggest contributes relapse via its actions extra-hypothalamic sites. present data, previous heroin- cocaine-trained point general role drugs stressors.