EFFECT OF ADRENALECTOMY ON THE INITIATION AND EXPRESSION OF COCAINE-INDUCED SENSITIZATION

The role of corticosterone in the initiation and expression phases of sensitization to cocaine was examined. To determine the effect of cort icosterone on the initiation of sensitization, male Sprague-Dawley rat s were given a sham adrenalectomy (ADX), or ADX surgery. Approximately 1 week later, rats were given a cocaine (15 mg/kg, IP) injection on d ay 1. On days 2-6, rats were given cocaine (30 mg/kg, IP), and the nex t day, a cocaine challenge (15 mg/kg) was administered (= early withdr awal). Four days later, 50% of the ADX rats were given corticosterone pellets and corticosterone in the evening drinking water to mimic the circadian variation in corticosterone levels. After 1 week, rats were given a final saline challenge followed by a cocaine challenge (15 mg/ kg) the next day (= late withdrawal). Locomotor activity was monitored after cocaine treatment on day 1 and after challenge at early and lat e withdrawal. Sham controls demonstrated a sensitized locomotor respon se to the cocaine challenge at early withdrawal, with a slight increas e in this behavioral sensitization at the late withdrawal time. In con trast, sensitization was not observed in ADX rats after early withdraw al from cocaine, but this attenuation was not permanent, since ADX ani mals demonstrated control levels of sensitization by the late withdraw al time 12 days later. Animals given corticosterone replacement 1 week prior to the late cocaine challenge also demonstrated a sensitized re sponse similar to control levels. The effect of corticosterone on the expression of sensitization was examined by administering daily cocain e as before followed by surgery a few days later. The treatment groups were sham, ADX and ADX+corticosterone replacement as described. Fourt een days later, a saline injection was given followed by a cocaine cha llenge the next day. Behavioral sensitization to a cocaine challenge w as found in all three treatment groups. These data suggest that adrena l hormones are necessary during the initiation phase of sensitization when observed after early withdrawal (1 day), but not when sensitizati on is examined at a later withdrawal time (12 days). In addition, cort icosterone levels do not significantly affect the expression phase of behavioral sensitization to cocaine.