N/OFQ-NOP System in Food Intake

  • Maria Vittoria Micioni Di Bonaventura
  • Emanuela Micioni Di Bonaventura
  • Carlo CifaniEmail author
  • Carlo Polidori
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 254)


While lifestyle modifications should be the first-line actions in preventing and treating obesity and eating disorders, pharmacotherapy also provides a necessary tool for the management of these diseases.

However, given the limitations of current anti-obesity drugs, innovative treatments that improve efficacy and safety are needed.

Since the discovery that the activation of the Nociceptin/Orphanin (N/OFQ) FQ peptide (NOP) receptor by N/OFQ induces an increase of food intake in laboratory animals, and the finding that this effect can be blocked by NOP antagonists, many NOP agonists and antagonists have been synthesized and tested in vitro and in vivo for their potential regulation of feeding behavior. Promising results seem to suggest that the N/OFQergic system may be a potential therapeutic target for the neural control of feeding behavior and related pathologies, especially in binge-like eating behavior.


Eating disorders Food intake N/OFQ Nociceptin/orphanin FQ Nociceptin/orphanin FQ peptide (NOP) receptor NOP agonist NOP antagonist Obesity 


  1. Agostini S, Petrella C (2014) The endogenous nociceptin/orphanin FQ-NOP receptor system as a potential therapeutic target for intestinal disorders. Neurogastroenterol Motil 26:1519–1526. CrossRefPubMedGoogle Scholar
  2. Agostini S, Eutamene H, Broccardo M, Improta G, Petrella C, Theodorou V, Bueno L (2009) Peripheral anti-nociceptive effect of nociceptin/orphanin FQ in inflammation and stress-induced colonic hyperalgesia in rats. Pain 141:292–299. CrossRefPubMedGoogle Scholar
  3. Amianto F, Ottone L, Abbate Daga G, Fassino S (2015) Binge-eating disorder diagnosis and treatment: a recap in front of DSM-5. BMC Psychiatry 15:70. CrossRefPubMedPubMedCentralGoogle Scholar
  4. Anton B, Fein J, To T, Li X, Silberstein L, Evans CJ (1996) Immunohistochemical localization of ORL-1 in the central nervous system of the rat. J Comp Neurol 368:229–251.<229::AID-CNE5>3.0.CO;2-5 CrossRefPubMedGoogle Scholar
  5. Blasio A et al (2013) Rimonabant precipitates anxiety in rats withdrawn from palatable food: role of the central amygdala. Neuropsychopharmacology 38:2498–2507. CrossRefPubMedPubMedCentralGoogle Scholar
  6. Bodnar RJ (1998) Recent advances in the understanding of the effects of opioid agents on feeding and appetite. Expert Opin Investig Drugs 7:485–497. CrossRefPubMedGoogle Scholar
  7. Bomberg EM, Grace MK, Levine AS, Olszewski PK (2006) Functional interaction between nociceptin/orphanin FQ and alpha-melanocyte-stimulating hormone in the regulation of feeding. Peptides 27:1827–1834. CrossRefPubMedGoogle Scholar
  8. Brookes ZL, Stedman EN, Guerrini R, Lawton BK, Calo G, Lambert DG (2007) Proinflammatory and vasodilator effects of nociceptin/orphanin FQ in the rat mesenteric microcirculation are mediated by histamine. Am J Phys Heart Circ Phys 293:H2977–H2985. CrossRefGoogle Scholar
  9. Bulik CM, Sullivan PF, Kendler KS (1998) Heritability of binge-eating and broadly defined bulimia nervosa. Biol Psychiatry 44:1210–1218. CrossRefPubMedGoogle Scholar
  10. Bulik CM, Sullivan PF, Kendler KS (2003) Genetic and environmental contributions to obesity and binge eating. Int J Eat Disord 33:293–298. CrossRefPubMedPubMedCentralGoogle Scholar
  11. Calo G, Guerrini R, Bigoni R, Rizzi A, Bianchi C, Regoli D, Salvadori S (1998) Structure-activity study of the nociceptin(1-13)-NH2 N-terminal tetrapeptide and discovery of a nociceptin receptor antagonist. J Med Chem 41:3360–3366. CrossRefPubMedGoogle Scholar
  12. Calo G et al (2011) UFP-112 a potent and long-lasting agonist selective for the nociceptin/orphanin FQ receptor. CNS Neurosci Ther 17:178–198. CrossRefPubMedGoogle Scholar
  13. Ciccocioppo R, Martin-Fardon R, Weiss F, Massi M (2001) Nociceptin/orphanin FQ inhibits stress- and CRF-induced anorexia in rats. Neuroreport 12:1145–1149. CrossRefPubMedGoogle Scholar
  14. Ciccocioppo R, Biondini M, Antonelli L, Wichmann J, Jenck F, Massi M (2002) Reversal of stress- and CRF-induced anorexia in rats by the synthetic nociceptin/orphanin FQ receptor agonist, Ro 64-6198. Psychopharmacology 161:113–119. CrossRefPubMedPubMedCentralGoogle Scholar
  15. Ciccocioppo R, Fedeli A, Economidou D, Policani F, Weiss F, Massi M (2003) The bed nucleus is a neuroanatomical substrate for the anorectic effect of corticotropin-releasing factor and for its reversal by nociceptin/orphanin FQ. J Neurosci 23:9445–9451. CrossRefPubMedPubMedCentralGoogle Scholar
  16. Cifani C, Polidori C, Melotto S, Ciccocioppo R, Massi M (2009) A preclinical model of binge eating elicited by yo-yo dieting and stressful exposure to food: effect of sibutramine, fluoxetine, topiramate, and midazolam. Psychopharmacology 204:113–125. CrossRefPubMedGoogle Scholar
  17. Cifani C, Di Bonaventura MVM, Ciccocioppo R, Massi M (2013) Binge eating in female rats induced by yo-yo dieting and stress. In: Avena NM (ed) Animal models of eating disorders. Springer, Berlin, pp 27–49CrossRefGoogle Scholar
  18. Costentin J, Florin S, Suaudeau C, Meunier JC (1998) [Cloning of prepronociceptin has led to the discovery of other biologically active peptides] Comptes rendus des seances de la Societe de biologie et de ses filiales 192:1099–1109Google Scholar
  19. Cottone P et al (2009) CRF system recruitment mediates dark side of compulsive eating. Proc Natl Acad Sci U S A 106:20016–20020. CrossRefPubMedPubMedCentralGoogle Scholar
  20. Cox BM, Christie MJ, Devi L, Toll L, Traynor JR (2015) Challenges for opioid receptor nomenclature: IUPHAR Review 9. Br J Pharmacol 172:317–323. CrossRefGoogle Scholar
  21. Cusin I, Rohner-Jeanrenaud F, Stricker-Krongrad A, Jeanrenaud B (1996) The weight-reducing effect of an intracerebroventricular bolus injection of leptin in genetically obese fa/fa rats. Reduced sensitivity compared with lean animals. Diabetes 45:1446–1450. CrossRefPubMedGoogle Scholar
  22. D’Addario C et al (2014) Endocannabinoid signaling and food addiction. Neurosci Biobehav Rev 47:203–224. CrossRefPubMedGoogle Scholar
  23. Dingemans AE, Bruna MJ, van Furth EF (2002) Binge eating disorder: a review. Int J Obes Relat Metab Disord 26:299–307. CrossRefPubMedGoogle Scholar
  24. Drewnowski A (1995) Metabolic determinants of binge eating. Addict Behav 20:733–745. CrossRefPubMedGoogle Scholar
  25. Economidou D, Policani F, Angellotti T, Massi M, Terada T, Ciccocioppo R (2006) Effect of novel NOP receptor ligands on food intake in rats. Peptides 27:775–783. CrossRefPubMedPubMedCentralGoogle Scholar
  26. Emmerson PJ, Miller RJ (1999) Pre- and postsynaptic actions of opioid and orphan opioid agonists in the rat arcuate nucleus and ventromedial hypothalamus in vitro. J Physiol 517(Pt 2):431–445. CrossRefPubMedPubMedCentralGoogle Scholar
  27. Farhang B, Pietruszewski L, Lutfy K, Wagner EJ (2010) The role of the NOP receptor in regulating food intake, meal pattern, and the excitability of proopiomelanocortin neurons. Neuropharmacology 59:190–200. CrossRefPubMedPubMedCentralGoogle Scholar
  28. Ferrari W (1958) Behavioural changes in animals after intracisternal injection with adrenocorticotrophic hormone and melanocyte-stimulating hormone. Nature 181:925–926. CrossRefPubMedGoogle Scholar
  29. Filaferro M et al (2014) Functional antagonism between nociceptin/orphanin FQ and corticotropin-releasing factor in rat anxiety-related behaviors: involvement of the serotonergic system. Neuropeptides 48:189–197. CrossRefPubMedGoogle Scholar
  30. Filippetti R, Kloting I, Massi M, Cifani C, Polidori C (2007) Involvement of cocaine-amphetamine regulated transcript in the differential feeding responses to nociceptin/orphanin FQ in dark agouti and Wistar Ottawa Karlsburg W rats. Peptides 28:1966–1973. CrossRefPubMedGoogle Scholar
  31. Foltin RW, Brady JV, Fischman MW (1986) Behavioral analysis of marijuana effects on food intake in humans. Pharmacol Biochem Behav 25:577–582. CrossRefPubMedGoogle Scholar
  32. Fullerton DT, Getto CJ, Swift WJ, Carlson IH (1985) Sugar, opioids and binge eating. Brain Res Bull 14:673–680. CrossRefPubMedGoogle Scholar
  33. Gavioli EC, Calo G (2006) Antidepressant- and anxiolytic-like effects of nociceptin/orphanin FQ receptor ligands. Naunyn Schmiedeberg’s Arch Pharmacol 372:319–330. CrossRefGoogle Scholar
  34. Giugliano D, Lefebvre PJ (1991) A role for beta-endorphin in the pathogenesis of human obesity? Horm Metab Res 23:251–256. CrossRefPubMedGoogle Scholar
  35. Gosnell BA, Levine AS, Morley JE (1986) The stimulation of food intake by selective agonists of mu, kappa and delta opioid receptors. Life Sci 38:1081–1088. CrossRefPubMedGoogle Scholar
  36. Guerrini R, Calo G, Bigoni R, Rizzi D, Regoli D, Salvadori S (2001) Structure-activity relationship of [Nphe1]-NC-(1-13)-NH2, a pure and selective nociceptin/orphanin FQ receptor antagonist. J Pept Res 57:215–222. CrossRefPubMedGoogle Scholar
  37. Guerrini R et al (2014) A novel and facile synthesis of tetra branched derivatives of nociceptin/orphanin FQ. Bioorg Med Chem 22:3703–3712. CrossRefPubMedGoogle Scholar
  38. Gunduz O et al (2006) In vitro and in vivo pharmacological characterization of the nociceptin/orphanin FQ receptor ligand Ac-RYYRIK-ol. Eur J Pharmacol 539:39–48. CrossRefPubMedGoogle Scholar
  39. Hardaway JA et al (2016) Nociceptin receptor antagonist SB 612111 decreases high fat diet binge eating. Behav Brain Res 307:25–34. CrossRefPubMedPubMedCentralGoogle Scholar
  40. Hardaway JA, Boyt K, Martin WJ, Wallace TL, Kash T (2018) Characterization of the nociceptin system in neural circuits underlying highly palatable food intake as a model of reward. Program No. 648.23. 2018 Neuroscience Meeting Planner. Society for Neuroscience, San Diego. OnlineGoogle Scholar
  41. Hashimoto Y, Calo G, Guerrini R, Smith G, Lambert DG (2000) Antagonistic effects of [Nphe1]nociceptin(1-13)NH2 on nociceptin receptor mediated inhibition of cAMP formation in Chinese hamster ovary cells stably expressing the recombinant human nociceptin receptor. Neurosci Lett 278:109–112. CrossRefPubMedGoogle Scholar
  42. Jenck F et al (2000) A synthetic agonist at the orphanin FQ/nociceptin receptor ORL1: anxiolytic profile in the rat. Proc Natl Acad Sci U S A 97:4938–4943. CrossRefPubMedPubMedCentralGoogle Scholar
  43. Joseph T et al (2006) Identification of mature nocistatin and nociceptin in human brain and cerebrospinal fluid by mass spectrometry combined with affinity chromatography and HPLC. Peptides 27:122–130. CrossRefPubMedGoogle Scholar
  44. Kaye WH, Pickar D, Naber D, Ebert MH (1982) Cerebrospinal fluid opioid activity in anorexia nervosa. Am J Psychiatry 139:643–645. CrossRefPubMedGoogle Scholar
  45. Koizumi M, Cagniard B, Murphy NP (2009) Endogenous nociceptin modulates diet preference independent of motivation and reward. Physiol Behav 97:1–13. CrossRefPubMedGoogle Scholar
  46. Lee YS et al (2008) Opioid and melanocortin receptors: do they have overlapping pharmacophores? Biopolymers 90:433–438. CrossRefPubMedPubMedCentralGoogle Scholar
  47. Leibowitz SF, Hor L (1982) Endorphinergic and alpha-noradrenergic systems in the paraventricular nucleus: effects on eating behavior. Peptides 3:421–428. CrossRefPubMedGoogle Scholar
  48. Leventhal L, Mathis JP, Rossi GC, Pasternak GW, Bodnar RJ (1998) Orphan opioid receptor antisense probes block orphanin FQ-induced hyperphagia. Eur J Pharmacol 349:R1–R3. CrossRefPubMedGoogle Scholar
  49. Margules DL, Moisset B, Lewis MJ, Shibuya H, Pert CB (1978) Beta-endorphin is associated with overeating in genetically obese mice (ob/ob) and rats (fa/fa). Science 202:988–991. CrossRefPubMedGoogle Scholar
  50. Matsushita H et al (2009) Chronic intracerebroventricular infusion of nociceptin/orphanin FQ produces body weight gain by affecting both feeding and energy metabolism in mice. Endocrinology 150:2668–2673. CrossRefPubMedGoogle Scholar
  51. McKay LD, Kenney NJ, Edens NK, Williams RH, Woods SC (1981) Intracerebroventricular beta-endorphin increases food intake of rats. Life Sci 29:1429–1434. CrossRefPubMedGoogle Scholar
  52. McLean S, Hoebel BG (1983) Feeding induced by opiates injected into the paraventricular hypothalamus. Peptides 4:287–292. CrossRefPubMedGoogle Scholar
  53. Meunier JC et al (1995) Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor. Nature 377:532–535. CrossRefGoogle Scholar
  54. Micioni Di Bonaventura MV, Cifani C, Lambertucci C, Volpini R, Cristalli G, Massi M (2012) A2A adenosine receptor agonists reduce both high-palatability and low-palatability food intake in female rats. Behav Pharmacol 23:567–574. CrossRefPubMedGoogle Scholar
  55. Micioni Di Bonaventura MV, Ubaldi M, Liberati S, Ciccocioppo R, Massi M, Cifani C (2013) Caloric restriction increases the sensitivity to the hyperphagic effect of nociceptin/orphanin FQ limiting its ability to reduce binge eating in female rats. Psychopharmacology 228:53–63. CrossRefPubMedGoogle Scholar
  56. Micioni Di Bonaventura MV et al (2014) Role of bed nucleus of the stria terminalis corticotrophin-releasing factor receptors in frustration stress-induced binge-like palatable food consumption in female rats with a history of food restriction. J Neurosci 34:11316–11324. CrossRefPubMedPubMedCentralGoogle Scholar
  57. Micioni Di Bonaventura MV, Ubaldi M, Giusepponi ME, Rice KC, Massi M, Ciccocioppo R, Cifani C (2017) Hypothalamic CRF1 receptor mechanisms are not sufficient to account for binge-like palatable food consumption in female rats. Int J Eat Disord 50:1194–1204. CrossRefPubMedGoogle Scholar
  58. Morley JE, Levine AS (1983) Involvement of dynorphin and the kappa opioid receptor in feeding. Peptides 4:797–800. CrossRefPubMedGoogle Scholar
  59. Morley JE, Levine AS, Yim GK, Lowy MT (1983) Opioid modulation of appetite. Neurosci Biobehav Rev 7:281–305. CrossRefPubMedGoogle Scholar
  60. Neal CR Jr, Mansour A, Reinscheid R, Nothacker HP, Civelli O, Akil H, Watson SJ Jr (1999) Opioid receptor-like (ORL1) receptor distribution in the rat central nervous system: comparison of ORL1 receptor mRNA expression with (125)I-[(14)Tyr]-orphanin FQ binding. J Comp Neurol 412:563–605.<563::AID-CNE2>3.0.CO;2-Z CrossRefGoogle Scholar
  61. Novelle MG, Dieguez C (2018) Food addiction and binge eating: lessons learned from animal models. Nutrients 10.
  62. Olszewski PK, Levine AS (2004) Minireview: characterization of influence of central nociceptin/orphanin FQ on consummatory behavior. Endocrinology 145:2627–2632. CrossRefPubMedGoogle Scholar
  63. Olszewski PK, Shaw TJ, Grace MK, Billington CJ, Levine AS (2000) Nocistatin inhibits food intake in rats. Brain Res 872:181–187. CrossRefPubMedGoogle Scholar
  64. Olszewski PK, Grace MK, Sanders JB, Billington CJ, Levine AS (2002) Effect of nociceptin/orphanin FQ on food intake in rats that differ in diet preference. Pharmacol Biochem Behav 73:529–535. CrossRefPubMedGoogle Scholar
  65. Olszewski PK et al (2010) Central nociceptin/orphanin FQ system elevates food consumption by both increasing energy intake and reducing aversive responsiveness. Am J Physiol Regul Integr Comp Physiol 299:R655–R663. CrossRefPubMedPubMedCentralGoogle Scholar
  66. Petrella C et al (2013) Protective and worsening peripheral nociceptin/orphanin FQ receptor-mediated effect in a rat model of experimental colitis. Pharmacol Res 70:72–79. CrossRefPubMedGoogle Scholar
  67. Pietras TA, Rowland NE (2002) Effect of opioid and cannabinoid receptor antagonism on orphanin FQ-induced hyperphagia in rats. Eur J Pharmacol 442:237–239. CrossRefPubMedGoogle Scholar
  68. Placidi RJ, Chandler PC, Oswald KD, Maldonado C, Wauford PK, Boggiano MM (2004) Stress and hunger alter the anorectic efficacy of fluoxetine in binge-eating rats with a history of caloric restriction. Int J Eat Disord 36:328–341. CrossRefPubMedGoogle Scholar
  69. Polidori C, Calo G, Ciccocioppo R, Guerrini R, Regoli D, Massi M (2000a) Pharmacological characterization of the nociceptin receptor mediating hyperphagia: identification of a selective antagonist. Psychopharmacology 148:430–437. CrossRefPubMedGoogle Scholar
  70. Polidori C, de Caro G, Massi M (2000b) The hyperphagic effect of nociceptin/orphanin FQ in rats. Peptides 21:1051–1062. CrossRefPubMedGoogle Scholar
  71. Pomonis JD, Billington CJ, Levine AS (1996) Orphanin FQ, agonist of orphan opioid receptor ORL1, stimulates feeding in rats. Neuroreport 8:369–371. CrossRefPubMedGoogle Scholar
  72. Pucci M et al (2016) Epigenetic regulation of nociceptin/orphanin FQ and corticotropin-releasing factor system genes in frustration stress-induced binge-like palatable food consumption. Addict Biol 21:1168–1185. CrossRefPubMedGoogle Scholar
  73. Reinscheid RK et al (1995) Orphanin FQ: a neuropeptide that activates an opioid-like G protein-coupled receptor. Science 270:792–794. CrossRefPubMedPubMedCentralGoogle Scholar
  74. Rinaldi-Carmona M et al (1994) SR141716A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Lett 350:240–244. CrossRefPubMedGoogle Scholar
  75. Rizzi A et al (2002) Pharmacological characterisation of [(pX)Phe4]nociceptin(1-13)NH2 analogues. 2. In vivo studies. Naunyn Schmiedeberg’s Arch Pharmacol 365:450–456. CrossRefGoogle Scholar
  76. Rizzi A et al (2007a) Pharmacological characterization of the nociceptin/orphanin FQ receptor antagonist SB-612111 [(-)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrah ydro-5H-benzocyclohepten-5-ol]: in vivo studies. J Pharmacol Exp Ther 321:968–974. CrossRefGoogle Scholar
  77. Rizzi A et al (2007b) In vitro and in vivo studies on UFP-112, a novel potent and long lasting agonist selective for the nociceptin/orphanin FQ receptor. Peptides 28:1240–1251. CrossRefPubMedPubMedCentralGoogle Scholar
  78. Rodi D, Zucchini S, Simonato M, Cifani C, Massi M, Polidori C (2008) Functional antagonism between nociceptin/orphanin FQ (N/OFQ) and corticotropin-releasing factor (CRF) in the rat brain: evidence for involvement of the bed nucleus of the stria terminalis. Psychopharmacology 196:523–531. CrossRefGoogle Scholar
  79. Sanger DJ, McCarthy PS (1982) The anorectic action of naloxone is attenuated by adaptation to a food-deprivation schedule. Psychopharmacology 77:336–338. CrossRefPubMedGoogle Scholar
  80. Schank JR, Ryabinin AE, Giardino WJ, Ciccocioppo R, Heilig M (2012) Stress-related neuropeptides and addictive behaviors: beyond the usual suspects. Neuron 76:192–208. CrossRefPubMedPubMedCentralGoogle Scholar
  81. Shaw WN, Mitch CH, Leander JD, Mendelsohn LG, Zimmerman DM (1991) The effect of the opioid antagonist LY255582 on body weight of the obese Zucker rat. Int J Obes 15:387–395PubMedGoogle Scholar
  82. Sobczak M, Cami-Kobeci G, Salaga M, Husbands SM, Fichna J (2014) Novel mixed NOP/MOP agonist BU08070 alleviates pain and inhibits gastrointestinal motility in mouse models mimicking diarrhea-predominant irritable bowel syndrome symptoms. Eur J Pharmacol 736:63–69. CrossRefPubMedPubMedCentralGoogle Scholar
  83. Statnick MA et al (2016) A novel nociceptin receptor antagonist LY2940094 inhibits excessive feeding behavior in rodents: a possible mechanism for the treatment of binge eating disorder. J Pharmacol Exp Ther 356:493–502. CrossRefPubMedPubMedCentralGoogle Scholar
  84. Stengel A, Tache Y (2014) CRF and urocortin peptides as modulators of energy balance and feeding behavior during stress. Front Neurosci 8:52. CrossRefPubMedPubMedCentralGoogle Scholar
  85. Stratford TR, Holahan MR, Kelley AE (1997) Injections of nociceptin into nucleus accumbens shell or ventromedial hypothalamic nucleus increase food intake. Neuroreport 8:423–426. CrossRefPubMedGoogle Scholar
  86. van den Brandt J, Kovacs P, Kloting I (2000a) Features of the metabolic syndrome in the spontaneously hypertriglyceridemic Wistar Ottawa Karlsburg W (RT1u Haplotype) rat. Metab Clin Exp 49:1140–1144. CrossRefPubMedGoogle Scholar
  87. van Den Brandt J, Kovacs P, Kloting I (2000b) Metabolic variability among disease-resistant inbred rat strains and in comparison with wild rats (Rattus norvegicus). Clin Exp Pharmacol Physiol 27:793–795. CrossRefGoogle Scholar
  88. Vergoni AV, Bertolini A (2000) Role of melanocortins in the central control of feeding. Eur J Pharmacol 405:25–32. CrossRefPubMedGoogle Scholar
  89. Vitale G, Arletti R, Ruggieri V, Cifani C, Massi M (2006) Anxiolytic-like effects of nociceptin/orphanin FQ in the elevated plus maze and in the conditioned defensive burying test in rats. Peptides 27:2193–2200. CrossRefPubMedGoogle Scholar
  90. Vitale G et al (2017) Effects of [Nphe(1), Arg(14), Lys(15)] N/OFQ-NH2 (UFP-101), a potent NOP receptor antagonist, on molecular, cellular and behavioural alterations associated with chronic mild stress. J Psychopharmacol 31:691–703. CrossRefPubMedGoogle Scholar
  91. Voisey J, Carroll L, van Daal A (2003) Melanocortins and their receptors and antagonists. Curr Drug Targets 4:586–597. CrossRefPubMedGoogle Scholar
  92. Wagner EJ, Ronnekleiv OK, Grandy DK, Kelly MJ (1998) The peptide orphanin FQ inhibits beta-endorphin neurons and neurosecretory cells in the hypothalamic arcuate nucleus by activating an inwardly-rectifying K+ conductance. Neuroendocrinology 67:73–82. CrossRefPubMedGoogle Scholar
  93. Wang L, Stengel A, Goebel M, Martinez V, Gourcerol G, Rivier J, Tache Y (2011) Peripheral activation of corticotropin-releasing factor receptor 2 inhibits food intake and alters meal structures in mice. Peptides 32:51–59. CrossRefPubMedGoogle Scholar
  94. Williams CM, Rogers PJ, Kirkham TC (1998) Hyperphagia in pre-fed rats following oral delta9-THC. Physiol Behav 65:343–346. CrossRefPubMedGoogle Scholar
  95. Witkin JM et al (2014) The biology of nociceptin/orphanin FQ (N/OFQ) related to obesity, stress, anxiety, mood, and drug dependence. Pharmacol Ther 141:283–299. CrossRefPubMedPubMedCentralGoogle Scholar
  96. Zaratin PF et al (2004) Modification of nociception and morphine tolerance by the selective opiate receptor-like orphan receptor antagonist (-)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahy dro-5H-benzocyclohepten-5-ol (SB-612111). J Pharmacol Exp Ther 308:454–461. CrossRefPubMedPubMedCentralGoogle Scholar
  97. Zaveri N (2003) Peptide and nonpeptide ligands for the nociceptin/orphanin FQ receptor ORL1: research tools and potential therapeutic agents. Life Sci 73:663–678. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Maria Vittoria Micioni Di Bonaventura
    • 1
  • Emanuela Micioni Di Bonaventura
    • 1
  • Carlo Cifani
    • 1
    Email author
  • Carlo Polidori
    • 1
  1. 1.School of Pharmacy, Pharmacology Unit, University of CamerinoCamerinoItaly

Personalised recommendations