NEUROENDOCRINE EFFECTS OF DEXMEDETOMIDINE - EVIDENCE OF CROSS-TOLERANCE BETWEEN A MU-OPIOID AGONIST AND AN ALPHA(2)-ADRENOCEPTOR AGONIST INGROWTH-HORMONE SECRETION OF THE MALE-RAT

The role of alpha(2)-adrenergic receptors (adrenoceptors) in the secre tion of growth hormone, prolactin and thyrotropin was studied using hi ghly selective agonists and antagonists of the alpha(2)-adrenoceptor. The interplay between opiates and alpha(2)-adrenergic drugs in the acu te secretion of growth hormone and prolactin, as well as the possible cross-tolerance between morphine (mu-opioid receptor agonist) and dexm edetomidine (alpha(2)-adrenoceptor agonist) in growth hormone secretio n were also evaluated. Dexmedetomidine dose-dependently increased plas ma growth hormone and prolactin levels and decreased thyrotropin level s. The enhanced secretion of both growth hormone and prolactin was ant agonized by atipamezole (an alpha(2)-adrenoceptor antagonist) but not by prazosin (an alpha(1)-adrenoceptor antagonist). Morphine (5 mg/kg)- induced stimulation of growth hormone secretion was antagonized by bot h naloxone (mu-opioid antagonist) and atipamezole. Naloxone, but not a tipamezole, antagonized the morphine-induced increase in prolactin sec retion. Dexmedetomidine increased growth hormone secretion in the sali ne pretreated rats, but did not do so in the morphine-tolerant rats. T he stimulation of alpha(2)-adrenoceptor enhances secretion of both gro wth hormone and prolactin. The adrenergic regulation of thyrotropin se cretion still remains unclear. Evidently, adrenergic mechanisms are in volved in the morphine-induced stimulation of growth hormone secretion , but not in the morphine-induced stimulation of prolactin secretion. In addition, there is a clear cross-tolerance between dexmedetomidine and morphine in growth hormone secretion of the rat.