SOCIAL ISOLATION-INDUCED ENHANCEMENT OF THE PSYCHOMOTOR EFFECTS OF MORPHINE DEPENDS ON CORTICOSTERONE SECRETION

Short-term social isolation has been shown to increase individual reactivity to addictive drugs, although the biological factors involved in this effect are largely unknown. In this study, we investigated the influence of corticosterone secretion on the effects of social isolation on the response to opioids. The effects of social isolation on morphine-induced locomotor activity were compared in: (i) animals with an intact hypothalamo-pituitary-adrenal (HPA) axis; (ii) animals in which stress-induced corticosterone secretion was blocked by adrenalectomy. The animals in the latter group were implanted with subcutaneous corticosterone pellets (50 mg), which slowly release corticosterone, producing stable plasma levels within the physiological range. Social isolation increased the locomotor response to morphine (2 mg/kg s.c.) in animals with an intact HPA axis, but not in animals in which corticosterone secretion was blocked. These results suggest that corticosterone secretion is required for the expression of the enhanced locomotor response to opioids induced by isolation. Since an enhanced locomotor reactivity to addictive drugs has been found to be frequently associated with an enhanced vulnerability to drug self-administration, these findings suggest a role for glucocorticoids in the vulnerability to the reinforcing effects of opioids.