Orphanin FQ/Nociceptin Is a Physiological Regulator of Prolactin Secretion in Female Rats

Abstract

Orphanin FQ/nociceptin (OFQ/N), the most recently identified endogenous opioid peptide, stimulates prolactin secretion in both male and female rats. OFQ/N, however, did not elicit this stimulatory effect through the mu-, delta-, or kappa-opiate receptor subtype. The role OFQ/N plays in prolactin regulation under physiological conditions and its mechanism of action are not known. The purpose of these studies was to determine the physiological significance and pharmacological specificity of the prolactin secretory response to OFQ/N. In addition, the role of the tuberoinfundibular dopaminergic (TIDA) neurons in mediating this response was examined. Opioid receptor-like-1 (ORL-1) receptors were blocked by pretreatment with compound B (Comp B), a purported OFQ/N antagonist, or receptor synthesis was disrupted by pretreatment with ORL-1 receptor antisense oligonucleotides. The prolactin secretory response to OFQ/N administration in diestrous females was measured. Furthermore, the suckling-induced prolactin response was also determined after Comp B pretreatment. TIDA neuronal activity was quantified in diestrous female rats to determine whether OFQ/N stimulates prolactin release by inhibiting TIDA neurons. OFQ/N significantly inhibited the TIDA neurons by 1 min, preceding the prolactin secretory response. Both Comp B and antisense pretreatment blocked the stimulatory effects of OFQ/N on prolactin release, and Comp B abolished the suckling-induced prolactin response. These studies indicate that OFQ/N is a potent stimulus for prolactin secretion in female rats and that it mediates this effect by rapid and transient inhibition of TIDA neuronal activity. Furthermore, OFQ/N plays a physiologically significant role in the regulation of prolactin secretion during lactation, and it mediates its effects via actions at the ORL-1 receptor subtype.

Endogenous Nociceptin System Involvement in Stress Responses and Anxiety Behavior

“…Acute N/OFQ action in behavioral tests may be influenced by an N/OFQ-induced hypolocomotor response that is subject to tolerance, thus recent behavioral studies have examined the impact of paired doses of N/OFQ to counteract the acute hypolocomotor effect. A further consideration is that just a handful of reports have considered sex effects on N/OFQ behavioral responses and there is a major bias toward the use of male animal models (Chesterfield et al, 2006). In female rats, however, neonatal handling does increase N/OFQ levels in periaqueductal gray (a midbrain defense region) (Ploj, Roman, Bergstrom, & Nylander, 2001), and N/OFQ induces lateral and central amygdala neuronal hyperpolarization (Meis & Pape, 1998) providing potential too for N/OFQ neuromodulation of aversion in females.…”

Role of hypothalamus nociceptin/orphanin FQ in pre-ovulatory luteinizing hormone surge of estrogen and progesterone-primed, ovariectomized rats

“…It has been demonstrated that OFQ activates the G-protein coupled, inwardly-rectifying K + channel and hyperpolarizes many hypothalamic neurosecretion cells, especially in the arcuate nucleus (ARC) [4] . OFQ administration stimulates prolactin and growth hormone release in a dose-and time-related manner [5] , and OFQ plays a physiologically significant role in the regulation of prolactin secretion [6] . A recent study has revealed that OFQ potently and dose-dependently inhibits forskolin-induced, gonadotropin-releasing hormone (GnRH) release from rat hypotha-lamic fragments [7] .…”

Orphanin FQ: Evidence for a Role in the Control of the Reproductive Neuroendocrine System

“…Functionally, OFQ has been implicated in a variety of systems including pain (5), anxiety (6), cardiovascular function (7), food intake (8), circadian rhythms (9), and cognition (10). There is also evidence that OFQ may play a role in neuroendocrine function: intracerebroventricular delivery of OFQ in the rat stimulates GH and prolactin (11,12) and has been reported to both stimulate (13) and inhibit (14) corticosterone secretion. Sinchak et al (15) have shown that OFQ delivered into the ventromedial nucleus facilitates lordosis in female rats in a dose-dependent manner.…”