It has been known for a number of years that mu-opioid receptor agonists (e.g., morphine, beta-endorphin, and enkephalin) inhibit luteinizing hormone (LH), vasopressin (VP), and oxytocin (OT) release and stimulate prolactin secretion in rodents and primates by an action at the level of the brain. Also, electrophysiological studies have established that hypothalamic neurons, including gonadotropin-releasing hormone (GnRH), VP, OT, beta-endorphin, and dopamine neurons, are responsive to mu-receptor activation. Although mu-receptor expression has been demonstrated in the hypothalamus, there have been few studies localizing these receptors in neurosecretory neurons. Therefore, we sought to document mu-opioid receptor mRNA expression in immunocytochemically identified hypothalamic neurons. The brains from both female and male guinea pigs were examined by using in situ hybridization and immunocytochemistry. The studies revealed that mu-receptor mRNA was expressed in different diencephalic regions including the preoptic area, the bed nuclei stria terminalis, the paraventricular nucleus thalamus, and the anterior hypothalamus, as well as the supraoptic (SON), paraventricular (PVH), ventromedial, dorsomedial, and arcuate nuclei of the hypothalamus. Importantly, mu-opioid receptors were expressed in subpopulations of GnRH neurons (33.25 +/- 4.6% and 33.6 +/- 3.7% in females and males, respectively), dopamine neurons (51.7 +/- 5.8% to 75.0 +/- 2.6%, depending on neuronal location), beta-endorphin neurons (68.3.0 +/- 4.4%), and VP neurons (41-70%, depending on neuronal location). Because mu-opioid receptors couple via G-proteins to activate inwardly rectifying potassium channels and to inhibit calcium channels, the presence of these receptors is likely to play a major role in directly controlling the excitability of hypothalamic neurons.
Copyright 2005 Wiley-Liss, Inc.