Elevation of glucocorticoids is necessary but not sufficient for the escalation of cocaine self-administration by chronic electric footshock stress in rats.

The examination of cocaine self-administration (SA) by rats under conditions that promote escalating patterns of intake should lead to a better understanding of factors that contribute to cocaine addiction. This study investigated the ability of repeated daily exposure to a stressor, electric footshock (EFS), to escalate cocaine SA. Male Sprague-Dawley rats were trained to self-administer cocaine (0.5 mg/kg/inf, i.v.) by pressing a lever under a FR4 schedule during 2-h sessions comprised of four 30-min SA components. Repeated daily EFS consisting of shock sequences (3 x 0.6 mA, 100-ms duration, 1-s frequency) delivered under a variable time 45-s schedule for 5 min before each of the four SA components across 14 days of SA testing produced a significant escalation of cocaine SA. EFS failed to escalate food-reinforced lever pressing and did not alter cocaine SA when administered either inside or outside of the SA context 4 h after daily SA testing. Surgical adrenalectomy along with diurnal corticosterone (CORT) replacement prevented EFS-induced escalation without altering SA in the absence of EFS, indicating that increases in circulating glucocorticoids were necessary for the escalating effects of EFS. Elevation of CORT through repeated daily CORT injections (3.0 mg/kg, i.p.) failed to reproduce the effects of repeated daily EFS on SA, but restored the escalating effects of EFS in adrenalectomized rats with CORT replacement, suggesting that an elevation of glucocorticoids was necessary but alone was not sufficient for the escalation of cocaine SA by EFS.