INTERMITTENT COCAINE EXPOSURE CAUSES DELAYED AND LONG-LASTING SENSITIZATION OF COCAINE-INDUCED ACTH-SECRETION IN RATS

In view of the possible role of the hypothalamux-pituitary-adrenal axi s 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 cocai ne exposure, the cocaine-induced increase of plasma adrenocorticotropi c hormone (ACTH) is unchanged, whereas after 14 days the ACTH response is enhanced 2-fold. The cocaine-induced increase of plasma corticoste rone is enhanced approximately 1.5-fold both 3 and 14 days after cocai ne withdrawal. Apparently, prior cocaine treatment causes a delayed se nsitization of cocaine-induced ACTH secretion and long-lasting cortico sterone hyper-responsiveness. We propose that the long-lasting changes in the hypothalamus-pituitary-adrenal axis may facilitate drug-induce d long-term behavioral sensitization.