Neuroendocrine Effects of Dexmedetomidine: Evidence of Cross-Tolerance Between a μ-Opioid Agonist and an α2-Adrenoceptor Agonist in Growth Hormone Secretion of the Male Rat

Abstract: The role of α₂-adrenergic receptors (adrenoceptors) in the secretion of growth hormone, prolactin and thyrotropin was studied using highly selective agonists and antagonists of the α₂-adrenoceptor. The interplay between opiates and α₂-adrenergic drugs in the acute secretion of growth hormone and prolactin, as well as the possible cross-tolerance between morphine (μ-opioid receptor agonist) and dexmedetomidine (α₂-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 α₂-adrenoceptor antagonist) but not by prazosin (an α₁-adrenoceptor antagonist). Morphine (5 mg/kg)-induced stimulation of growth hormone secretion was antagonized by both naloxone (u-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 α₂-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.