Altered Responsivity to Central Administrations of Corticotropin-Releasing Factor in Rats With a History of Opiate Exposures

The authors studied the effects of a history of opiate exposures on behavioral responses to intracerebroventricular (ICV) microinjections of the stress-related peptide corticotropin-releasing factor (CRF). Rats were injected for 10 days with morphine (10 mg/kg) or saline, and 1 or 7 days later they received an ICV microinjection of CRF (0.5 μg or 2.5 μg) or artificial cerebrospinal fluid. Microinjections of CRF produced anxiety-like behavior, locomotor activity, and self-grooming. The anxiogenic response was altered so that morphine-treated rats showed reduced responses to 0.5-μg CRF but showed exaggerated responses to 2.5-μg CRF 1 or 7 days after last opiate exposure. These findings suggest that alterations in central CRF circuits may underpin the increased vulnerability to anxiety observed following opiate exposures.