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Vol. 289, Issue 3, 1641-1647, June 1999

Effects of Self-Administered Cocaine on Plasma Adrenocorticotropic Hormone and Cortisol in Male Rhesus Monkeys1

Jillian H. Broadbear, Gail Winger, Theodore J. Cicero and James H. Woods

Departments of Psychology (J.H.B., J.H.W.) and Pharmacology (G.W., J.H.W.), University of Michigan Medical School, Ann Arbor, Michigan; and Department of Psychiatry (T.J.C.), Washington University, St. Louis, Missouri

This study was designed to examine the effects of self-administered cocaine on hypothalamic-pituitary-adrenal (HPA) axis activity in rhesus monkeys. Initially, basal release of cortisol and adrenocorticotropic hormone (ACTH) was measured in singly housed male and female monkeys (n = 9) over a 24-h period using plasma samples obtained from indwelling venous catheters. Basal cortisol and ACTH levels in both male and female rhesus monkeys demonstrated a circadian pattern of release, with peak levels for cortisol (19.60 ± 2.16 µg/dl) and ACTH (19.63 ± 2.56 pg/ml) measured at 6:00 AM. The nadir for ACTH (6.27 ± 0.62 pg/ml) occurred at 6:00 PM, preceding the cortisol nadir (5.55 ± 1.21 µg/dl) at 9:00 PM. The reinforcing effects of saline, 0.01, 0.03, 0.1, and 0.3 mg/kg/injection cocaine were then evaluated using a fixed-ratio 30, time-out 10-min schedule of reinforcement in seven male monkeys. Blood was sampled before, during, and after self-administration sessions. Self-administration of cocaine produced dose-dependent increases in cortisol and ACTH. One dose of cocaine (0.03 mg/kg/injection), although reliably self-administered, did not produce a significant increase in HPA axis activity. These results indicate that although cocaine dose-dependently increases HPA axis activity, the HPA effect is more likely a consequence of overall cocaine intake than it is an indicator of cocaine doses that are sufficient to maintain self-administration behavior.

0022-3565/99/2893-1641$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics


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