Figure 1. Stress potentiates cocaine-induced drug-seeking behavior by a corticosterone-dependent, GR-independent mechanism. A, B, Cocaine lever responses on the last day of extinction and during reinstatement testing of (A) adrenal-intact (n = 7) or (B) adrenalectomized (ADX; n = 6) rats. On the day of reinstatement testing, rats were subjected to 15 min of uncontrollable, intermittent electric footshock (EFS) or no shock, followed by injection of cocaine (2.5 mg/kg, i.p.) or saline, and cocaine lever responses were recorded for 2 h. C, Cocaine lever responses on the last day of extinction and during reinstatement testing. Rats (n = 6) received an injection of corticosterone (CORT; 2.0 mg/kg, i.p.) or vehicle, followed 40 min later by an injection of cocaine (2.5 mg/kg, i.p.) or saline. D, Cocaine lever responses on the last day of extinction and during reinstatement testing. Rats (n = 10) received an injection of the glucocorticoid receptor antagonist RU38486 (12.5 mg/kg, s.c.) or vehicle, followed 60 min later by injection of corticosterone (2.0 mg/kg, i.p.) or vehicle, followed 40 min later by an injection of cocaine (2.5 mg/kg, i.p.) (see also Table 1). *p < 0.05, significantly different from extinction responding. Error bars represent mean ± SEM.