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MCH Receptor 1 Antagonists: Antidepressant/Anxiolytic Potential in Animal Models

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Melanin-Concentrating Hormone and Sleep

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Abstract

Melanin-concentrating hormone (MCH), a cyclic 19-amino acid neuropeptide, has been involved in a variety of physiological events, including the regulation of stress responses and mood. Two subtypes of MCH receptor, MCH1 and MCH2, have been identified, and MCH1 mediates most of the physiological functions of MCH.

To date, numerous non-peptidic MCH1 antagonists have been developed, and studies using these MCH1 antagonists and genetically manipulated mice lacking MCH1 have revealed that the blockade of MCH1 produces antidepressant and anxiolytic effects in a variety of rodent models. In addition, the mechanisms underlying the antidepressant/anxiolytic effects of MCH1 antagonists have been investigated, and the regulation of the hypothalamus-pituitary-adrenal axis activity, mesolimbic dopaminergic system, and serotonergic system may be responsible for the stress-coping and mood-modulating effects of MCH1 antagonists. Importantly, MCH1 antagonists showed a faster onset of action, compared with currently available medications, and a smaller number of side effects, compared with conventional antidepressants and anxiolytic treatments. Therefore, MCH1 antagonists may enable improved treatment for depression and anxiety disorders and deserve further investigation, particularly in clinical trials, as potential new treatments for these disorders.

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References

  • Alt A, Nisenbaum ES, Bleakman D, Witkin JM (2006) A role for AMPA receptors in mood disorders. Biochem Pharmacol 71:1273–1288

    Article  CAS  PubMed  Google Scholar 

  • Bächner D, Kreienkamp H, Weise C, Buck F, Richter D (1999) Identification of melanin concentrating hormone (MCH) as the natural ligand for the orphan somatostatin-like receptor 1 (SLC-1). FEBS Lett 457:522–524

    Article  PubMed  Google Scholar 

  • Basso AM, Bratcher NA, Gallagher KB, Cowart MD, Zhao C, Sun M, Esbenshade TA, Brune ME, Fox GB, Schmidt M, Collins CA, Souers AJ, Iyengar R, Vasudevan A, Kym PR, Hancock AA, Rueter LE (2006) Lack of efficacy of melanin-concentrating hormone-1 receptor antagonists in models of depression and anxiety. Eur J Pharmacol 540:115–120

    Article  CAS  PubMed  Google Scholar 

  • Berton O, Nestler EJ (2006) New approaches to antidepressant drug discovery: beyond monoamines. Nat Rev Neurosci 7:137–151

    Article  CAS  PubMed  Google Scholar 

  • Bittencourt JC, Presse F, Arias C, Peto C, Vaughan J, Nahon JL, Vale W, Sawchenko PE (1992) The melanin-concentrating hormone system of the rat brain: an immuno- and hybridization histochemical characterization. J Comp Neurol 319:218–245

    Article  CAS  PubMed  Google Scholar 

  • Borowsky B, Durkin MM, Ogozalek K, Marzabadi MR, DeLeon J, Lagu B, Heurich R, Lichtblau H, Shaposhnik Z, Daniewska I, Blackburn TP, Branchek TA, Gerald C, Vaysse PJ, Forray C (2002) Antidepressant, anxiolytic and anorectic effects of a melanin-concentrating hormone-1 receptor antagonist. Nat Med 8:825–830

    Article  CAS  PubMed  Google Scholar 

  • Borsini F, Podhorna J, Marazziti D (2002) Do animal models of anxiety predict anxiolytic-like effects of antidepressants? Psychopharmacology 163:121–141

    Article  CAS  PubMed  Google Scholar 

  • Chaki S, Nakazato A, Kennis L, Nakamura M, Mackie C, Sugiura M, Vinken P, Ashton D, Langlois X, Steckler T (2004) Anxiolytic- and antidepressant-like profile of a new CRF1 receptor antagonist, R278995/CRA0450. Eur J Pharmacol 485:145–158

    Article  CAS  PubMed  Google Scholar 

  • Chaki S, Funakoshi T, Hirota-Okuno S, Nishiguchi M, Shimazaki T, Iijima M, Grottick AJ, Kanuma K, Omodera K, Sekiguchi Y, Okuyama S, Tran TA, Semple G, Thomsen W (2005) Anxiolytic- and antidepressant-like profile of ATC0065 and ATC0175: nonpeptidic and orally active melanin-concentrating hormone receptor 1 antagonists. J Pharmacol Exp Ther 313:831–839

    Article  CAS  PubMed  Google Scholar 

  • Chaki S, Shimazaki T, Nishiguchi M, Funakoshi T, Iijima M, Ito A, Kanuma K, Sekiguchi Y (2015) Antidepressant/anxiolytic potential and adverse effect liabilities of melanin-concentrating hormone receptor 1 antagonists in animal models. Pharmacol Biochem Behav 135:154–168

    Article  CAS  PubMed  Google Scholar 

  • Chambers J, Ames RS, Bergsma D, Muir A, Fitzgerald LR, Hervieu G, Dytko GM, Foley JJ, Martin J, Liu WS, Park J, Ellis C, Ganguly S, Konchar S, Cluderay J, Leslie R, Wilson S, Sarau HM (1999) Melanin-concentrating hormone is the cognate ligand for the orphan G-protein-coupled receptor SLC-1. Nature 400:261–265

    Article  CAS  PubMed  Google Scholar 

  • David DJ, Klemenhagen KC, Holick KA, Saxe MD, Mendez I, Santarelli L, Craig DA, Zhong H, Swanson CJ, Hegde LG, Ping XI, Dong D, Marzabadi MR, Gerald CP, Hen R (2007) Efficacy of the MCHR1 antagonist N-[3-(1-{[4-(3,4-difluorophenoxy)phenyl]methyl}(4-piperidyl))-4-methylphenyl]-2-methylpropanamide (SNAP 94847) in mouse models of anxiety and depression following acute and chronic administration is independent of hippocampal neurogenesis. J Pharmacol Exp Ther 321:237–248

    Article  CAS  PubMed  Google Scholar 

  • Detke MJ, Rickels M, Lucki I (1995) Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants. Psychopharmacology 121:66–72

    Article  CAS  PubMed  Google Scholar 

  • Devera A, Pascovich C, Lagos P, Falconi A, Sampogna S, Chase MH, Torterolo P (2015) Melanin-concentrating hormone (MCH) modulates the activity of dorsal raphe neurons. Brain Res 1598:114–128

    Article  CAS  PubMed  Google Scholar 

  • Diorio D, Viau V, Meaney MJ (1993) The role of the medial prefrontal cortex (cingulate gyrus) in the regulation of hypothalamic-pituitary-adrenal responses to stress. J Neurosci 13:3839–3847

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fernandes C, File SE (1999) Dizocilpine does not prevent the development of tolerance to the anxiolytic effects of diazepam in rats. Brain Res 815:431–434

    Article  CAS  PubMed  Google Scholar 

  • File SE, Seth P (2003) A review of 25 years of the social interaction test. Eur J Pharmacol 463:35–53

    Article  CAS  PubMed  Google Scholar 

  • Fried S, O'Neill K, Hawes BE (2002) Cloning and characterization of rhesus monkey MCH-R1 and MCH-R2. Peptides 23:1401–1408

    Article  CAS  PubMed  Google Scholar 

  • García-Fuster MJ, Parks GS, Clinton SM, Watson SJ, Akil H, Civelli O (2012) The melanin-concentrating hormone (MCH) system in an animal model of depression-like behavior. Eur Neuropsychopharmacol 22:607–613

    Article  PubMed  Google Scholar 

  • Gehlert DR, Rasmussen K, Shaw J, Li X, Ardayfio P, Craft L, Coskun T, Zhang HY, Chen Y, Witkin JM (2009) Preclinical evaluation of melanin-concentrating hormone receptor 1 antagonism for the treatment of obesity and depression. J Pharmacol Exp Ther 329:429–438

    Article  CAS  PubMed  Google Scholar 

  • Georgescu D, Sears RM, Hommel JD, Barrot M, Bolaños CA, Marsh DJ, Bednarek MA, Bibb JA, Maratos-Flier E, Nestler EJ, DiLeone RJ (2005) The hypothalamic neuropeptide melanin-concentrating hormone acts in the nucleus accumbens to modulate feeding behavior and forced-swim performance. J Neurosci 25:2933–2940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gonzalez MI, Vaziri S, Wilson CA (1996) Behavioral effects of alpha-MSH and MCH after central administration in the female rat. Peptides 17:171–177

    Article  CAS  PubMed  Google Scholar 

  • Griebel G, Holsboer F (2012) Neuropeptide receptor ligands as drugs for psychiatric diseases: the end of the beginning? Nat Rev Drug Discov 11:462–478

    Article  CAS  PubMed  Google Scholar 

  • Hervieu GJ, Cluderay JE, Harrison D, Meakin J, Maycox P, Nasir S, Leslie RA (2000) The distribution of the mRNA and protein products of the melanin-concentrating hormone (MCH) receptor gene, slc-1, in the central nervous system of the rat. Eur J Neurosci 12:1194–1216

    Article  CAS  PubMed  Google Scholar 

  • Iijima M, Yoshimizu T, Shimazaki T, Tokugawa K, Fukumoto K, Kurosu S, Kuwada T, Sekiguchi Y, Chaki S (2014) Antidepressant and anxiolytic profiles of newly synthesized arginine vasopressin V1B receptor antagonists: TASP0233278 and TASP0390325. Br J Pharmacol 171:3511–3525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jezová D, Bartanusz V, Westergren I, Johansson BB, Rivier J, Vale W, Rivier C (1992) Rat melanin-concentrating hormone stimulates adrenocorticotropin secretion: evidence for a site of action in brain regions protected by the blood-brain barrier. Endocrinology 130:1024–1029

    PubMed  Google Scholar 

  • Kawauchi H, Kawazoe I, Tsubokawa M, Kishida M, Baker BI (1983) Characterization of melanin-concentrating hormone in chum salmon pituitaries. Nature 305:321–323

    Article  CAS  PubMed  Google Scholar 

  • Kela J, Salmi P, Rimondini-Giorgini R, Heilig M, Wahlestedt C (2003) Behavioural analysis of melanin-concentrating hormone in rats: evidence for orexigenic and anxiolytic properties. Regul Pept 114:109–114

    Article  CAS  PubMed  Google Scholar 

  • Kennedy AR, Todd JF, Dhillo WS, Seal LJ, Ghatei MA, O'Toole CP, Jones M, Witty D, Winborne K, Riley G, Hervieu G, Wilson S, Bloom SR (2003) Effect of direct injection of melanin-concentrating hormone into the paraventricular nucleus: further evidence for a stimulatory role in the adrenal axis via SLC-1. J Neuroendocrinol 15:268–272

    Article  CAS  PubMed  Google Scholar 

  • Knapp RJ, Goldenberg R, Shuck C, Cecil A, Watkins J, Miller C, Crites G, Malatynska E (2002) Antidepressant activity of memory-enhancing drugs in the reduction of submissive behavior model. Eur J Pharmacol 440:27–35

    Article  CAS  PubMed  Google Scholar 

  • Knigge KM, Wagner JE (1997) Melanin-concentrating hormone (MCH) involvement in pentylenetetrazole (PTZ)-induced seizure in rat and guinea pig. Peptides 18:1095–1097

    Article  CAS  PubMed  Google Scholar 

  • Kolakowski LF Jr, Jung BP, Nguyen T, Johnson MP, Lynch KR, Cheng R, Heng HH, George SR, O’Dowd BF (1996) Characterization of a human gene related to genes encoding somatostatin receptors. FEBS Lett 398:253–258

    Article  CAS  PubMed  Google Scholar 

  • Kym PR, Iyengar R, Souers AJ, Lynch JK, Judd AS, Gao J, Freeman J, Mulhern M, Zhao G, Vasudevan A, Wodka D, Blackburn C, Brown J, Che JL, Cullis C, Lai SJ, LaMarche MJ, Marsilje T, Roses J, Sells T, Geddes B, Govek E, Patane M, Fry D, Dayton BD, Brodjian S, Falls D, Brune M, Bush E, Shapiro R, Knourek-Segel V, Fey T, McDowell C, Reinhart GA, Preusser LC, Marsh K, Hernandez L, Sham HL, Collins CA (2005) Discovery and characterization of aminopiperidinecoumarin melanin concentrating hormone receptor 1 antagonists. J Med Chem 48:5888–5891

    Article  CAS  PubMed  Google Scholar 

  • Lagos P, Urbanavicius J, Scorza MC, Miraballes R, Torterolo P (2011) Depressive-like profile induced by MCH microinjections into the dorsal raphe nucleus evaluated in the forced swim test. Behav Brain Res 218:259–266

    Article  CAS  PubMed  Google Scholar 

  • Lee C, Parks GS, Civelli O (2011) Anxiolytic effects of the MCH1R antagonist TPI 1361-17. J Mol Neurosci 43:132–137

    Article  CAS  PubMed  Google Scholar 

  • Lembo PM, Grazzini E, Cao J, Hubatsch DA, Pelletier M, Hoffert C, St-Onge S, Pou C, Labrecque J, Groblewski T, O’Donnell D, Payza K, Ahmad S, Walker P (1999) The receptor for the orexigenic peptide melanin-concentrating hormone is a G-protein-coupled receptor. Nat Cell Biol 1:267–271

    Article  CAS  PubMed  Google Scholar 

  • Licinio J, Wong ML, Gold PW (1996) The hypothalamic-pituitary-adrenal axis in anorexia nervosa. Psychiatry Res 62:75–83

    Article  CAS  PubMed  Google Scholar 

  • Millan MJ, Gobert A, Panayi F, Rivet JM, Dekeyne A, Brocco M, Ortuno JC, Di Cara B (2008) The melanin-concentrating hormone1 receptor antagonists, SNAP-7941 and GW3430, enhance social recognition and dialysate levels of acetylcholine in the frontal cortex of rats. Int J Neuropsychopharmacol 11:1105–1122

    Article  CAS  PubMed  Google Scholar 

  • Monzón ME, De Barioglio SR (1999) Response to novelty after i.c.v. injection of melanin-concentrating hormone (MCH) in rats. Physiol Behav 67:813–817

    Article  PubMed  Google Scholar 

  • Monzon ME, de Souza MM, Izquierdo LA, Izquierdo I, Barros DM, de Barioglio SR (1999) Melanin-concentrating hormone (MCH) modifies memory retention in rats. Peptides 20:1517–1519

    Article  CAS  PubMed  Google Scholar 

  • Nagasaki H, Chung S, Dooley CT, Wang Z, Li C, Saito Y, Clark SD, Houghten RA, Civelli O (2009) The pharmacological properties of a novel MCH1 receptor antagonist isolated from combinatorial libraries. Eur J Pharmacol 602:194–202

    Article  CAS  PubMed  Google Scholar 

  • Nemeroff CB (1996) The corticotropin-releasing factor (CRF) hypothesis of depression: new findings and new directions. Mol Psychiatry 1:336–342

    CAS  PubMed  Google Scholar 

  • Okuyama S, Chaki S, Kawashima N, Suzuki Y, Ogawa S, Nakazato A, Kumagai T, Okubo T, Tomisawa K (1999) Receptor binding, behavioral, and electrophysiological profiles of nonpeptide corticotropin-releasing factor subtype 1 receptor antagonists CRA1000 and CRA1001. J Pharmacol Exp Ther 289:926–935

    CAS  PubMed  Google Scholar 

  • Parks GS, Okumura SM, Gohil K, Civelli O (2010) Mice lacking Melanin Concentrating Hormone 1 receptor are resistant to seizures. Neurosci Lett 484:104–107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pissios P, Frank L, Kennedy AR, Porter DR, Marino FE, Liu FF, Pothos EN, Maratos-Flier E (2008) Dysregulation of the mesolimbic dopamine system and reward in MCH−/− mice. Biol Psychiatry 64:184–191

    Article  CAS  PubMed  Google Scholar 

  • Rasmusson AM, Vythilingam M, Morgan CA 3rd (2003) The neuroendocrinology of posttraumatic stress disorder: new directions. CNS Spectr 8:651–656, 665–667

    Article  PubMed  Google Scholar 

  • Rocca P, Fonzo V, Scotta M, Zanalda E, Ravizza L (1997) Paroxetine efficacy in the treatment of generalized anxiety disorder. Acta Psychiatr Scand 95:444–450

    Article  CAS  PubMed  Google Scholar 

  • Roche KW, O’Brien RJ, Mammen AL, Bernhardt J, Huganir RL (1996) Characterization of multiple phosphorylation sites on the AMPA receptor GluR1 subunit. Neuron 16:1179–1188

    Article  CAS  PubMed  Google Scholar 

  • Rorick-Kehn LM, Witkin JM, Statnick MA, Eberle EL, McKinzie JH, Kahl SD, Forster BM, Wong CJ, Li X, Crile RS, Shaw DB, Sahr AE, Adams BL, Quimby SJ, Diaz N, Jimenez A, Pedregal C, Mitch CH, Knopp KL, Anderson WH, Cramer JW, McKinzie DL (2014) LY2456302 is a novel, potent, orally-bioavailable small molecule kappa-selective antagonist with activity in animal models predictive of efficacy in mood and addictive disorders. Neuropharmacology 77:131–144

    Article  CAS  PubMed  Google Scholar 

  • Roy M, David NK, Danao JV, Baribault H, Tian H, Giorgetti M (2006) Genetic inactivation of melanin-concentrating hormone receptor subtype 1 (MCHR1) in mice exerts anxiolytic-like behavioral effects. Neuropsychopharmacology 31:112–120

    Article  CAS  PubMed  Google Scholar 

  • Roy M, David N, Cueva M, Giorgetti M (2007) A study of the involvement of melanin-concentrating hormone receptor 1 (MCHR1) in murine models of depression. Biol Psychiatry 61:174–180

    Article  CAS  PubMed  Google Scholar 

  • Sailer AW, Sano H, Zeng Z, McDonald TP, Pan J, Pong SS, Feighner SD, Tan CP, Fukami T, Iwaasa H, Hreniuk DL, Morin NR, Sadowski SJ, Ito M, Ito M, Bansal A, Ky B, Figueroa DJ, Jiang Q, Austin CP, MacNeil DJ, Ishihara A, Ihara M, Kanatani A, Van der Ploeg LH, Howard AD, Liu Q (2001) Identification and characterization of a second melanin-concentrating hormone receptor, MCH-2R. Proc Natl Acad Sci USA 98:7564–7569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saito Y, Nothacker HP, Wang Z, Lin SH, Leslie F, Civelli O (1999) Molecular characterization of the melanin-concentrating-hormone receptor. Nature 400:265–269

    Article  CAS  PubMed  Google Scholar 

  • Saito Y, Cheng M, Leslie FM, Civelli O (2001) Expression of the melanin-concentrating hormone (MCH) receptor mRNA in the rat brain. J Comp Neurol 435:26–40

    Article  CAS  PubMed  Google Scholar 

  • Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, Weisstaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R (2003) Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 301:805–809

    Article  CAS  PubMed  Google Scholar 

  • Sears RM, Liu RJ, Narayanan NS, Sharf R, Yeckel MF, Laubach M, Aghajanian GK, DiLeone RJ (2010) Regulation of nucleus accumbens activity by the hypothalamic neuropeptide melanin-concentrating hormone. J Neurosci 30:8263–8273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shimazaki T, Iijima M, Chaki S (2006a) The pituitary mediates the anxiolytic-like effects of the vasopressin V1B receptor antagonist, SSR149415, in a social interaction test in rats. Eur J Pharmacol 543:63–67

    Article  CAS  PubMed  Google Scholar 

  • Shimazaki T, Yoshimizu T, Chaki S (2006b) Melanin-concentrating hormone MCH1 receptor antagonists: a potential new approach to the treatment of depression and anxiety disorders. CNS Drugs 20:801–811

    Article  CAS  PubMed  Google Scholar 

  • Shimomura Y, Mori M, Sugo T, Ishibashi Y, Abe M, Kurokawa T, Onda H, Nishimura O, Sumino Y, Fujino M (1999) Isolation and identification of melanin-concentrating hormone as the endogenous ligand of the SLC-1 receptor. Biochem Biophys Res Commun 261:622–626

    Article  CAS  PubMed  Google Scholar 

  • Shirayama Y, Chaki S (2006) Neurochemistry of the nucleus accumbens and its relevance to depression and antidepressant action in rodents. Curr Neuropharmacol 4:277–291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shirayama Y, Ishida H, Iwata M, Hazama GI, Kawahara R, Duman RS (2004) Stress increases dynorphin immunoreactivity in limbic brain regions and dynorphin antagonism produces antidepressant-like effects. J Neurochem 90:1258–1268

    Article  CAS  PubMed  Google Scholar 

  • Smith DG, Tzavara ET, Shaw J, Luecke S, Wade M, Davis R, Salhoff C, Nomikos GG, Gehlert DR (2005) Mesolimbic dopamine super-sensitivity in melanin-concentrating hormone-1 receptor-deficient mice. J Neurosci 25:914–922

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith DG, Davis RJ, Rorick-Kehn L, Morin M, Witkin JM, McKinzie DL, Nomikos GG, Gehlert DR (2006) Melanin-concentrating hormone-1 receptor modulates neuroendocrine, behavioral, and corticolimbic neurochemical stress responses in mice. Neuropsychopharmacology 31:1135–1145

    Article  CAS  PubMed  Google Scholar 

  • Smith DG, Hegde LG, Wolinsky TD, Miller S, Papp M, Ping X, Edwards T, Gerald CP, Craig DA (2009) The effects of stressful stimuli and hypothalamic-pituitary-adrenal axis activation are reversed by the melanin-concentrating hormone 1 receptor antagonist SNAP 94847 in rodents. Behav Brain Res 197:284–291

    Article  CAS  PubMed  Google Scholar 

  • Spooren WP, Schoeffter P, Gasparini F, Kuhn R, Gentsch C (2002) Pharmacological and endocrinological characterisation of stress-induced hyperthermia in singly housed mice using classical and candidate anxiolytics (LY314582, MPEP and NKP608). Eur J Pharmacol 435:161–170

    Article  CAS  PubMed  Google Scholar 

  • Takekawa S, Asami A, Ishihara Y, Terauchi J, Kato K, Shimomura Y, Mori M, Murakoshi H, Kato K, Suzuki N, Nishimura O, Fujino M (2002) T-226296: a novel, orally active and selective melanin-concentrating hormone receptor antagonist. Eur J Pharmacol 438:129–135

    Article  CAS  PubMed  Google Scholar 

  • Tan CP, Sano H, Iwaasa H, Pan J, Sailer AW, Hreniuk DL, Feighner SD, Palyha OC, Pong SS, Figueroa DJ, Austin CP, Jiang MM, Yu H, Ito J, Ito M, Ito M, Guan XM, MacNeil DJ, Kanatani A, Van der Ploeg LH, Howard AD (2002) Melanin-concentrating hormone receptor subtypes 1 and 2: species-specific gene expression. Genomics 79:785–792

    Article  CAS  PubMed  Google Scholar 

  • Tichomirowa MA, Keck ME, Schneider HJ, Paez-Pereda M, Renner U, Holsboer F, Stalla GK (2005) Endocrine disturbances in depression. J Endocrinol Investig 28:89–99

    Article  CAS  Google Scholar 

  • Tye KM, Mirzabekov JJ, Warden MR, Ferenczi EA, Tsai HC, Finkelstein J, Kim SY, Adhikari A, Thompson KR, Andalman AS, Gunaydin LA, Witten IB, Deisseroth K (2013) Dopamine neurons modulate neural encoding and expression of depression-related behaviour. Nature 493:537–541

    Article  CAS  PubMed  Google Scholar 

  • Urbanavicius J, Lagos P, Torterolo P, Scorza C (2014) Prodepressive effect induced by microinjections of MCH into the dorsal raphe: time course, dose dependence, effects on anxiety-related behaviors, and reversion by nortriptyline. Behav Pharmacol 25:316–324

    Article  CAS  PubMed  Google Scholar 

  • Urbanavicius J, Lagos P, Torterolo P, Abin-Carriquiry JA, Scorza C (2016) Melanin-concentrating hormone projections to the dorsal raphe nucleus: an immunofluorescence and in vivo microdialysis study. J Chem Neuroanat 72:16–24

    Article  CAS  PubMed  Google Scholar 

  • Vale W, Spiess J, Rivier C, Rivier J (1981) Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science 213:1394–1397

    Article  CAS  PubMed  Google Scholar 

  • Varas MM, Pérez MF, Ramírez OA, de Barioglio SR (2003) Increased susceptibility to LTP generation and changes in NMDA-NR1 and -NR2B subunits mRNA expression in rat hippocampus after MCH administration. Peptides 24:1403–1411

    Article  CAS  PubMed  Google Scholar 

  • Vasudevan A, Souers AJ, Freeman JC, Verzal MK, Gao J, Mulhern MM, Wodka D, Lynch JK, Engstrom KM, Wagaw SH, Brodjian S, Dayton B, Falls DH, Bush E, Brune M, Shapiro RD, Marsh KC, Hernandez LE, Collins CA, Kym PR (2005) Aminopiperidine indazoles as orally efficacious melanin concentrating hormone receptor-1 antagonists. Bioorg Med Chem Lett 15:5293–5297

    Article  CAS  PubMed  Google Scholar 

  • Vaughan JM, Fischer WH, Hoeger C, Rivier J, Vale W (1989) Characterization of melanin-concentrating hormone from rat hypothalamus. Endocrinology 125:1660–1665

    Article  CAS  PubMed  Google Scholar 

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  1. Research Headquarters, Taisho Pharmaceutical Co., Ltd., Saitama, Saitama, Japan

    Shigeyuki Chaki

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  1. Somnogen Canada Inc. , Toronto, Ontario, Canada

    S. R. Pandi-Perumal

  2. Department of Physiology, School of Medicine, University of the Republic, Montevideo, Uruguay

    Pablo Torterolo

  3. Department of Pharmacology and Therapeutics, School of Medicine Clinics Hospital, University of the Republic, Montevideo, Uruguay

    Jaime M. Monti

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Chaki, S. (2018). MCH Receptor 1 Antagonists: Antidepressant/Anxiolytic Potential in Animal Models. In: Pandi-Perumal, S., Torterolo, P., Monti, J. (eds) Melanin-Concentrating Hormone and Sleep . Springer, Cham. https://doi.org/10.1007/978-3-319-75765-0_12

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