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.
Schmidt
E D
ED
Graduate School Neurosciences Amsterdam, Research Institute Neurosciences Vrije Universiteit, Faculty of Medicine, Department of Pharmacology, Netherlands.
Tilders
F J
FJ
Janszen
A W
AW
Binnekade
R
R
De Vries
T J
TJ
Schoffelmeer
A N
AN
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003345:Corticosterone / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D011388:Prolactin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D003042:Cocaine; D003345:Corticosterone