Intermittent cocaine exposure causes delayed and long-lasting sensitization of cocaine-induced ACTH secretion in rats

In view of the possible role of the hypothalamus-pituitary-adrenal axis in the long-term effects of drugs of abuse, we studied the response of the hypothalamus-pituitary-adrenal axis to cocaine challenges 3 and 14 days after cocaine withdrawal. Three days after intermittent cocaine exposure, the cocaine-induced increase of plasma adrenocorticotropic hormone (ACTH) is unchanged, whereas after 14 days the ACTH response is enhanced 2-fold. The cocaine-induced increase of plasma corticosterone is enhanced approximately 1.5-fold both 3 and 14 days after cocaine withdrawal. Apparently, prior cocaine treatment causes a delayed sensitization of cocaine-induced ACTH secretion and long-lasting corticosterone hyper-responsiveness. We propose that the long-lasting changes in the hypothalamus-pituitary-adrenal axis may facilitate drug-induced long-term behavioral sensitization.