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 corticosterone on the initiation of sensitization, male Sprague-Dawley rats were given a sham adrenalectomy (ADX), or ADX surgery. Approximately 1 week later, rats were given a cocaine (15 mg/kg, i.p.) injection on day 1. On days 2-6, rats were given cocaine (30 mg/kg, i.p.), and the next day, a cocaine challenge (15 mg/kg) was administered (= early withdrawal). 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 late withdrawal. Sham controls demonstrated a sensitized locomotor response to the cocaine challenge at early withdrawal, with a slight increase in this behavioral sensitization at the late withdrawal time. In contrast, sensitization was not observed in ADX rats after early withdrawal from cocaine, but this attenuation was not permanent, since ADX animals demonstrated control levels of sensitization by the late withdrawal time 12 days later. Animals given corticosterone replacement 1 week prior to the late cocaine challenge also demonstrated a sensitized response similar to control levels. The effect of corticosterone on the expression of sensitization was examined by administering daily cocaine as before followed by surgery a few days later. The treatment groups were sham, ADX and ADX+corticosterone replacement as described. Fourteen days later, a saline injection was given followed by a cocaine challenge the next day. Behavioral sensitization to a cocaine challenge was found in all three treatment groups. These data suggest that adrenal hormones are necessary during the initiation phase of sensitization when observed after early withdrawal (1 day), but not when sensitization is examined at a later withdrawal time (12 days). In addition, corticosterone levels do not significantly affect the expression phase of behavioral sensitization to cocaine.