Effect of adrenalectomy and corticosterone on cocaine-induced sensitization in rats

Effects of adrenalectomy (ADX) and corticosterone (CORT) on the development and expression of sensitization to the locomotor effect of cocaine (COC) w ere studied in rats. Sensitization was evoked by 5 daily injections of COC (10 mg/kg) and measured after a challenge dose of the drug (10 mg/kg) after a 5-day withdrawal (on day 10 of the experiment). ADX, performed before th e start of COC administration, completely blocked the manifestation of COC- induced sensitization. In contrast, ADX performed on animals already sensit ized to COC did not affect the sensitized locomotor activity response to a challenge dose of COC (on day 18). Pretreatment with CORT, 10 mg/kg, but no t 5 mg/kg, before each of the 5 daily COC injections facilitated the develo pment of COC sensitization, tested after a 5-day withdrawal. When pretreate d with CORT alone (10 mg/kg), the challenge dose of COC administered on day 10 induced cross-sensitization to CORT. CORT (10 mg/kg) injected acutely b efore COC on day 10, potentiated the expression of COC sensitization. When given alone, on day 10 CORT (5-10 mg/kg) induced an increase in the locomot or activity of rats pretreated daily (5 injections) with COC No drug treatm ent induced conditioned locomotion, as measured after saline challenge on d ay 8. Our results indicate that CORT facilitates the development and expres sion of COC sensitization, while ADX blocks the initiation of the behaviora l phenomenon only. Moreover, there takes place cross-sensitization between CORT and COC, which indicates a close relationship between the drug-related mechanism and behavioral sensitization.