Neuroendocrine effects of dexmedetomidine: evidence of cross-tolerance between a mu-opioid agonist and an alpha 2-adrenoceptor agonist in growth hormone secretion of the male rat.

Abstract

The role of alpha 2-adrenergic receptors (adrenoceptors) in the secretion of growth hormone, prolactin and thyrotropin was studied using highly selective agonists and antagonists of the alpha 2-adrenoceptor. The interplay between opiates and alpha 2-adrenergic drugs in the acute secretion of growth hormone and prolactin, as well as the possible cross-tolerance between morphine (mu-opioid receptor agonist) and dexmedetomidine (alpha 2-adrenoceptor agonist) in growth hormone secretion were also evaluated. Dexmedetomidine dose-dependently increased plasma growth hormone and prolactin levels and decreased thyrotropin levels. The enhanced secretion of both growth hormone and prolactin was antagonized 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 both naloxone (mu-opioid antagonist) and atipamezole. Naloxone, but not atipamezole, antagonized the morphine-induced increase in prolactin secretion. Dexmedetomidine increased growth hormone secretion in the saline pretreated rats, but did not do so in the morphine-tolerant rats. The stimulation of alpha 2-adrenoceptor enhances secretion of both growth hormone and prolactin. The adrenergic regulation of thyrotropin secretion still remains unclear. Evidently, adrenergic mechanisms are involved 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.