ACUTE BLOCKADE OF CORTICOSTERONE SECRETION DECREASES THE PSYCHOMOTOR STIMULANT EFFECTS OF COCAINE

Previous reports have shown that long-term blockade of corticosterone secretion, by either adrenalectomy or repeated treatment with an inhib itor of corticosterone synthesis, metyrapone, profoundly reduces sensi tivity to drugs of abuse. In this report we investigated whether acute blockade of corticosterone secretion hits similar effects. Animals re ceived, a single injection of metyrapone (50 mg/kg SC) and were tested for their locomotor response to cocaine (15 mg/kg IP) 3 hours later. Acute metyrapone treatment reduced the locomotor response to cocaine b y about 50%, and this effect was reversed by corticosterone (20 mg/kg SC). The behavioral effects of these treatments paralleled changes in plasma corticosterone levels 20 minutes after an injection of cocaine. Despite the differences in behavior and corticosterone levels, the br ain levels of cocaine in these groups did not differ. These results in dicate that the behavioral effects of cocaine can be modified by an ac ute pharmacological manipulation of corticosterone secretion. (C) 1997 American College of Neuropsychopharmacology Neuropsychopharmacology 1 6:156-161, 1997]