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

E. Donné Schmidt, Fred J.H. Tilders, Anton W.J.W. Janszen, R. Binnekade, Taco J. De Vries, Anton N.M. Schoffelmeer

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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.

Original languageEnglish
Pages (from-to)317-321
Number of pages5
JournalEuropean journal of pharmacology
Issue number3
Publication statusPublished - 24 Oct 1995


  • ACTH (adrenocorticotropic hormone)
  • Cocaine
  • Corticosterone
  • Hypothalamus-pituitary-adrenal axis

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