EFFECTS OF COCAINE ON PULSATILE ACTIVITY OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN MALE RHESUS-MONKEYS - NEUROENDOCRINE AND BEHAVIORAL-CORRELATES

Cocaine stimulates the hypothalamic-pituitary-adrenal (HPA) axis in ro dents and in humans, This study examined the acute effects of cocaine (0.4 and 0.8 mg/kg) and saline placebo on pulsatile adrenocorticotropi c hormone (ACTH) and cortisol release in seven male rhesus monkeys, Pu lsatile ACTH and cortisol release were evaluated with an intensive (2- min) venous blood sampling procedure and cluster analysis. In addition , the behavioral responses to cocaine were analyzed to assess the rela tionship between HPA axis activation and behavior. Although analysis o f group data revealed significant (P < .05) increases in pulse amplitu de and incremental peak height of ACTH and cortisol release after coca ine (0.8 mg/kg) administration, examination of individual data indicat ed that this effect was not consistent across all monkeys. Cocaine (0. 8 mg/kg) increased ACTH plasma levels within 4.7 +/- 1.3 min (P < .05) and amplitude-related characteristics (P < .05) of pulsatile ACTH and cortisol release only in those animals that subsequently showed behav ioral stimulation (high responders: n = 3). The frequency of pulsatile ACTH and cortisol release remained unchanged by cocaine. Cocaine (0.8 mg/kg) decreased the mean amplitude of ACTH peaks with no changes in pulsatile cortisol release in the four monkeys that showed no behavior al stimulation (low responders). These differences in pulsatile ACTH a nd cortisol release patterns after cocaine could not be explained by d ifferent plasma cocaine levels. Peak plasma cocaine levels averaged 63 .1 +/- 13.4 and 78.0 +/- 21.4 ng/ml within 2 min after lower dose and 183.3 +/- 52.3 and 204.3 +/- 50.8 ng/ml after higher dose of cocaine i n high- and low responder groups, respectively (P > .05; N.S.). Base-l ine cortisol, but not ACTH, levels were higher (P < .05) in low respon ders before administration of 0.8 mg/kg of cocaine. Peak and valley ch aracteristics of base-line cortisol release were higher in low respond ers than in high responders and an inverse relationship was found betw een basal cortisol levels and postcocaine ACTH release and behavior. I n summary, cocaine stimulated the pulsatile ACTH and cortisol release by increasing the amplitude of secretory episodes in behaviorally resp onsive monkeys.