EFFECTS OF COCAINE AND CORTICOTROPIN-RELEASING FACTOR ON PULSATILE ACTH AND CORTISOL RELEASE IN OVARIECTOMIZED RHESUS-MONKEYS

Cocaine stimulates ACTH secretion by a corticotropin-releasing factor (CRF)-dependent mechanism in male rats, rhesus monkeys, and humans. To determine the generality of this effect, we examined the effects of a cute cocaine administration on the pulsatile release of ACTH and corti sol in three ovariectomized (OVX) rhesus monkeys and compared its effe cts to stimulation with CRF. Venous blood samples were collected at 2- min intervals for 60 min before and after iv administration of cocaine (0.4 and 0.8 mg/kg) and CRF (1.0 and 10 mu g/kg). Cluster analysis pr ocedures were used to evaluate the pul satile characteristics of ACTH and cortisol release. After placebo administration, an ACTH pulse freq uency of 3 peaks/h was detected. After cocaine administration, plasma cocaine levels peaked at 92 +/- 3.0 and 201 +/- 60 ng/mL within 2 min. However, in contrast to normal intact males, cocaine did not stimulat e the pulsatile release of ACTH in OVX females. Cocaine (0.4 mg/kg) de creased ACTH incremental peak height and valley levels compared with p re-cocaine values, and a higher dose of cocaine produced no changes in ACTH release. Bolus injection of a low dose of CRF (1.0 mu g/kg, iv) significantly increased ACTH incremental peak height (P < 0.05), and a higher dose of CRF (10 mu g/kg) increased ACTH peak amplitude, percen tage increase in peak amplitude, area under the peaks, and incremental peak heights as well as ACTH valley level and nadir (10 mu g/kg, iv) (P < 0.05). ACTH pulse frequency did not change after CRF or cocaine a dministration. Pulsatile release of cortisol was 2.7 peaks/h under pla cebo conditions and did not change after cocaine or CRF administration . Cortisol pulse amplitude was increased after low and high doses of C RF. High doses of CRF (10 mu g/kg) also increased the mean level of co rtisol valleys. In summary, we found that CRF but not cocaine stimulat ed pulsatile ACTH and cortisol release in OVX rhesus monkeys. The prof ound ACTH response to CRF challenge suggests that the CRF sensitivity and the ACTH release capacity of the anterior pituitary corticotroph c ells were intact. The lack of stimulatory effects of cocaine on the hy pothalamic-pituitary-adrenal axis in OVX monkeys, in contrast to norma l male monkeys, may reflect the absence of gonadal steroids.