Prior, repeated exposure to cocaine potentiates locomotor responsivity to central injections of corticotropin-releasing factor (CRF) in rats

Rationale. There is considerable evidence that the stress-related neuropeptide, corticotropin-releasing factor (CRF), plays an important role in mediating behavioural changes induced by prior experience with cocaine. From this perspective, it is conceivable that repeated exposure to cocaine induces a form of sensitization in CRF systems that makes animals more responsive to CRF following prolonged drug-free periods. Objectives. To study the effects of repeated cocaine exposure on locomotor activity induced by different doses of CRF after drug-free periods ranging from 24 h to 28 days. Methods. Male Wistar rats were injected once daily for 7 days with cocaine (15 mg/kg, IP on days 1 and 7 in locomotor chambers; 30 mg/kg, IP, on days 2-6 in home cages) or saline. In experiment 1, starting 10 days after the last injection, animals were tested for their locomotor response to intracerebroventricular (ICV) injections of vehicle and three doses of CRF (0.25, 0.5, and 5 mug). In experiment 2, animals were tested for their locomotor response to ICV injections of 0.5 mug CRF after drug-free periods of 1-2, 10-11 and 28-29 days. Results. Compared to saline pre-exposed animals, cocaine pre-exposed animals showed a significantly greater locomotor response to CRF, relative to vehicle, at all doses tested (experiment 1) and after drug-free periods of up to 28 days (experiment 2). The effects were clear and extremely consistent in magnitude between experiments and conditions. Conclusions. These results suggest that cocaine pre-exposure induces long-term changes in the responsivity of the central nervous system to CRF.