RESTORATION OF ACTH CORTISOL AND LH RESPONSES TO NALOXONE BY CHRONIC DOPAMINERGIC TREATMENT IN PARKINSONS-DISEASE

Naloxone is unable to stimulate ACTH/cortisol secretion in patients wi th de novo Parkinson's disease, suggesting a reduced endogenous opioid control of the hypothalamic-pituitary-adrenal axis in parkinsonian pa tients. In the present study we examined whether Parkinson's disease a lso impairs the secretion of LH, which is under the inhibitory control of different opioid peptides than ACTH/cortisol. In addition, we exam ined whether a chronic dopaminergic therapy for at least one year with levodopa (450 mg/day) plus benserazide (112.5 mg/day) in 3 divided or al doses/day of Madopar modifies the ACTH/cortisol and/or the LH respo nse to naloxone (4 mg as an i.v. bolus plus 10 mg infused in 2 hours). Ten parkinsonian patients (aged 52-62 years) and 8 normal controls (5 0-60 years) were tested with naloxone and in a different occasion with normal saline. The parkinsonian patients were tested both before and after dopaminergic treatment. Tests started at 09.00 h and lasted 2.5 hours. Basal ACTH/cortisol and LH levels were similar in all groups. D uring saline tests, ACTH/cortisol levels showed a slight physiological decline in all groups, whereas LH levels remained constant. Naloxone administration significantly increased the plasma levels of ACTH/corti sol and LH in the normal controls, but not in the parkinsonian patient s before the dopaminergic treatment. In contrast, dopaminergic therapy restored significant ACTH/cortisol and LH responses to naloxone in pa rkinsonian patients. In fact, after levodopa plus benserazide, naloxon e-induced ACTH, cortisol and LH increments in parkinsonian patients we re significantly higher than before therapy and were indistinguishable from those observed in the normal controls. These data suggest that i n men Parkinson's-related dopaminergic alterations may underlie the de fective endogenous opioid control of ACTH/cortisol and LH secretion.