HIGH-DOSE NALOXONE (1.0 MG KG) - PSYCHOLOGICAL AND ENDOCRINE EFFECTS IN NORMAL-MALE SUBJECTS PRETREATED WITH ONE MILLIGRAM OF DEXAMETHASONE/

The possible participation of the endogenous opioid system (EOS) in th e negative feedback of the hypothalamic-pituirary-adrenal axis (HPA-a) activated by low doses (1 mg) of dexamethasone (Dex) was investigated . Ten male healthy subjects (mean age 31.5 +/- 1.9 SEM) were studied o n 2 separate days, in a double-blind, cross-over and placebo-controlle d design. All subjects were pretreated with 1.0 mg Dex orally the nigh t (2300h) before both test days. On the study days, subjects were admi tted at 0700h for cannula insertion; the administration of an IV bolus of either naloxone (Nal) (1.0 mg/kg) or saline solution (Sal) IV was started at 0900h. Before and following each infusion, mood was measure d by a Visual Analogue Scales (VAS) and by the Affective Quality Scale (AQS) every 30 min and blood samples were taken at 15-min intervals. Blood pressure and heart rate were also monitored. Before Dex administ ration, plasma cortisol levels were within the normal range in all sub jects (210.4 +/- 13 ng/ml), while after 9 h after Dex cortisol levels showed the expected significant (p < 0.01) decrease (11.5 +/- 1.9 and 15.04 +/- 0.7 ng/ml for Sal and Nal test days respectively). There wer e no detectable increases in plasma cortisol levels following either N al nor Sal administration. However, there was a Nal-induced significan t increase in LH (p < 0.01) thus indicating that an effective opioid b lockade at the level of the hypothalamic-pituitary unit occurred. Ther e were also a mild and selective Dex + Nal-induced dysphoric (mood fac tors related to subjects perception of their cognition) and bradycardi c effects (p < 0.05). These results suggest that the EOS is not direct ly involved in the negative feedback triggered by low doses of Dex of the HPA-a, and that there might be a possible glucocorticoid-opioid in teraction for the modulation of some aspects of mood. (C) 1998 Elsevie r Science Ltd. All rights reserved.