Elsevier

Neuroscience

Volume 115, Issue 2, 2 December 2002, Pages 637-643
Neuroscience

Orphanin FQ-induced hyperphagia is mediated by corticosterone and central glucocorticoid receptors

https://doi.org/10.1016/S0306-4522(02)00290-7Get rights and content

Abstract

Orphanin FQ (Nociceptin) has been reported to stimulate food intake in satiated rats and to stimulate corticosterone release. A large body of evidence exists to link central feeding systems with the regulation of corticosterone. In this study, we sought to determine whether or not circulating corticosterone is necessary for the induction of food intake by Orphanin FQ. We found that intracerebroventricular injection of Orphanin FQ (0.64–5 nmoles) dose dependently stimulated food intake and plasma corticosterone within 30 min of injection. Removal of corticosterone, by adrenalectomy, abolished the hyperphagic effect of Orphanin FQ. The stimulatory effect of Orphanin FQ on food intake was still negated following a low dose of corticosterone replacement (corresponding to a plasma corticosterone concentration of 1.86±0.99 μg/dl). However, following a larger dose of corticosterone replacement (corresponding to a plasma corticosterone concentration of 8.92±0.55 μg/dl) the feeding effect was fully restored. We concluded this study by testing the glucocorticoid receptor antagonist, RU486 (Mifepristone, 80 μg/2 μl) on Orphanin FQ-induced feeding. Central injection of RU486, 30 min prior to injection of Orphanin FQ, significantly reduced Orphanin FQ-induced food intake in comparison to vehicle-treated controls. Overall, these data demonstrate the necessity for circulating corticosterone in the mediation of Orphanin-FQ-induced feeding and suggest that the mechanism through which the hyperphagic effect is obtained involves activation of central glucocorticoid receptors.

Section snippets

Experimental procedures

Male Sprague–Dawley rats (∼250 g) (Charles River Laboratories, Wilmington, MA, USA), were housed three per cage, under conditions of constant temperature and humidity, with ad libitum access to food and water. Animals were maintained on a 12-h light/dark cycle, with lights on at 06.00 h, and were allowed to habituate to the housing room for 4 days prior to surgery. All procedures described were approved by the University of Michigan Committee on Use and Care of Animals and the National

Results

I.c.v. injection of N/OFQ dose-dependently increased food intake within 30 min of injection. Vehicle-treated animals consumed very little food during this time and with each increasing dose of N/OFQ there was a corresponding increase in food intake (Fig. 1A). In the same animals, and within the same time frame, a stimulatory effect of N/OFQ was also found on plasma corticosterone (Fig. 1B).

In the adrenalectomy study, as expected, N/OFQ had a stimulatory effect on food intake in sham-operated

Discussion

This study has replicated previous reports of the stimulatory effect of N/OFQ on food intake (Pomonis et al., 1996, Nicholson et al., 1997, Stratford et al., 1997) and on corticosterone release (Devine et al., 2001). It has demonstrated, for the first time, the necessity for circulating corticosterone for N/OFQ-induced food intake. Thus, we conclude that N/OFQ-induced food intake requires the activation of central GR receptors that play a permissive role in its orexigenic effects.

In the first

References (28)

  • C. Polidori et al.

    The hyperphagic effect of Nociceptin/Orphanin FQ in rats

    Peptides

    (2000)
  • B.G. Stanley et al.

    Suppression of neuropeptide Y-elicited eating by adrenalectomy or hypophysectomy: reversal with corticosterone

    Brain Res.

    (1989)
  • D.L. Tempel et al.

    Diurnal variations in the feeding responses to norepinephrine, neuropeptide Y and galanin in the PVN

    Brain Res. Bull.

    (1990)
  • P. Bhakthavatsalam et al.

    Alpha-2-noradrenergic feeding rhythm in paraventricular nucleus: relation to corticosterone

    Am. J. Physiol.

    (1986)
  • Cited by (37)

    • Nociceptin/orphanin FQ receptor system blockade as an innovative strategy for increasing resilience to stress

      2021, Peptides
      Citation Excerpt :

      By contrast, chronic stress modulates the N/OFQ system but in an individual manner, thus being correlated to behavioral responses, and possibly linked to the mechanisms involved in resilience/vulnerability to stress. As summarized in Table 2, icv and intra-BNST injection of N/OFQ in naïve rats stimulates the increase in plasma corticosterone and adrenocorticotropic hormone (ACTH) levels [18,32–37], and corticotropin-releasing factor (CRF) mRNA in paraventricular hypothalamic nucleus and pro-opiomelanocortin (POMC) mRNA in the anterior pituitary [38]. If N/OFQ is injected in mildly stressed rats a significant increase of circulating stress hormones is still detected [39], but after a more significant stressful event, such as immobilization and LPS-injection, plasma corticosterone levels are not increased further [18,40].

    • Targeting opioid dysregulation in depression for the development of novel therapeutics

      2019, Pharmacology and Therapeutics
      Citation Excerpt :

      Activation of the N/OFQ system at the level of the hypothalamus is necessary for adaptation to novelty or mild stressors. Central administration of N/OFQ and other NOP agonists elevated circulating levels of corticosterone and ACTH in stress naïve rodents in a dose-dependent manner (Devine, Watson, & Akil, 2001; Fernandez et al., 2004; Leggett et al., 2006; Nicholson et al., 2002). Furthermore, NOP agonists enhanced the secretion of these stress hormones in rats following exposure to novelty novel environment, but not in rats exposed to restraint, a more severe stressor (Devine et al., 2001).

    • Nociceptin/Orphanin FQ-NOP Receptor System in Inflammatory and Immune-Mediated Diseases

      2015, Vitamins and Hormones
      Citation Excerpt :

      However, a crucial point to consider is whether plasma cortisol concentrations are a relevant marker of immune suppression, since it is not clear whether plasma cortisol concentrations are increased in patients with depressed immune function (Al-Hashimi et al., 2013). In rodents, the acute administration of N/OFQ generally increases ACTH and glucocorticoids; this may have immunosuppressive actions (Devine, Watson, & Akil, 2001; Fernandez, Misilmeri, Felger, & Devine, 2004; Green, Barbieri, Brown, Chen, & Devine, 2007; Leggett, Harbuz, Jessop, & Fulford, 2006; Nicholson, Akil, & Watson, 2002; Vitale, Arletti, Ruggieri, Cifani, & Massi, 2006). However, opposite effects have also been reported (Le Cudennec, Naudin, Do Rego, & Costentin, 2002).

    View all citing articles on Scopus
    View full text