μ‐opioid receptor mRNA expression in identified hypothalamic neurons

Abstract

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.

Limited effects of β-endorphin compared to loperamide or fentanyl in a neuroendocrine biomarker assay in non-human primates

“…This confirms that in primates, μ-agonist induced prolactin release can be mediated by sites located functionally outside the blood-brain barrier (Wardlaw et al, 1980;Zheng et al, 2005). Prior studies, primarily in rodents, report that μ-receptor mRNA or protein can be detected in areas involved in the control of prolactin release, including the arcuate nucleus, and median eminence (e.g., Beauvillain et al, 1992;Zheng et al, 2005). These are also the first studies to detect a prolactinreleasing effect of loperamide per se, in humans or non-human primates, to our knowledge (e.g., at i.v.…”

Molecular mechanisms that drive estradiol-dependent burst firing of Kiss1 neurons in the rostral periventricular preoptic area

“…GIRK channels are critical for driving the membrane potential into the hyperpolarized state necessary to de-inactivate the Ca V 3 channels underlying the T-current. The majority of hypothalamic neurons express GABA B and opioid receptors, which are coupled to GIRK channels, and Kiss1 neurons in the RP3V are no exception (present findings; 21,25,28,51,57). In fact, these cells express -, -, and ␦-opioid receptor transcripts, and the vast majority of these cells respond to -and -agonists.…”

“…Opioid receptors are coupled to GIRK channels, and activation of GIRK channels can facilitate rebound burst firing (4, 50). The vast majority of hypothalamic neurons express opioid receptors, and -and ␦-opioid receptors are coupled to GIRK channels (21,25,28,51,57). Thus, we argue that rebound burst firing of Kiss1 neurons in the RP3V is facilitated by opioidergic afferents that operate through one or more of the classical opioid receptors expressed by these Kiss1 neurons.…”

Gonadotropin-Releasing Hormone Neurons Express KATPChannels That Are Regulated by Estrogen and Responsive to Glucose and Metabolic Inhibition

“…However, it is believed that metabolic signals are transmitted to GnRH neurons via the area postrema and the mediobasal hypothalamus (Wade and Jones, 2004;The ESHRE Capri Workshop Group, 2006). Mediobasal hypothalamic POMC and NPY neurons project directly onto GnRH to modulate GnRH neuronal activity through -opioid and NPY5 receptors, respectively (Lagrange et al, 1995;Campbell et al, 2001;Zheng et al, 2005). However, until now, there has been little evidence that GnRH neurons respond directly to metabolic factors such as glucose.…”