INHIBITION OF CORTICOSTERONE SYNTHESIS BY METYRAPONE DECREASES COCAINE-INDUCED LOCOMOTION AND RELAPSE OF COCAINE SELF-ADMINISTRATION

Several studies have recently shown that basal and stress-induced secr etion of corticosterone may enhance vulnerability to drugs of abuse. I n this report, we studied the effects of metyrapone, an inhibitor of t he synthesis of corticosterone, on cocaine-induced locomotion and on t he relapse of cocaine self-administration. Locomotor response to cocai ne was studied because psychomotor effects of drugs have been shown to be related to their reinforcing properties. Self-administration was s tudied in the relapse phase since blockade of relapse is central to th e therapy of addiction. Before these behavioral tests, rats in differe nt experimental groups were injected subcutaneously with either metyra pone (100 mg/kg) or vehicle, twice a day for 8 days. Metyrapone treatm ent reduced cocaine-induced locomotor activity and relapse of cocaine self-administration, without inducing a nonspecific disruption of moto r or food-directed behaviors. Under these experimental conditions, the metyrapone treatment totally blocked stress-induced corticosterone se cretion but did not modify basal corticosterone levels. These results confirm the involvement of glucococorticoids in the pathophysiological mechanisms underlying vulnerability to drug abuse, and may have impli cations for the development of new therapeutic strategies of drug addi ction.