1932

Abstract

Melatonin, or 5-methoxy--acetyltryptamine, is synthesized and released by the pineal gland and locally in the retina following a circadian rhythm, with low levels during the day and elevated levels at night. Melatonin activates two high-affinity G protein–coupled receptors, termed MT and MT, to exert beneficial actions in sleep and circadian abnormality, mood disorders, learning and memory, neuroprotection, drug abuse, and cancer. Progress in understanding the role of melatonin receptors in the modulation of sleep and circadian rhythms has led to the discovery of a novel class of melatonin agonists for treating insomnia, circadian rhythms, mood disorders, and cancer. This review describes the pharmacological properties of a slow-release melatonin preparation (i.e., Circadin®) and synthetic ligands (i.e., agomelatine, ramelteon, tasimelteon), with emphasis on identifying specific therapeutic effects mediated through MT and MT receptor activation. Discovery of selective ligands targeting the MT or the MT melatonin receptors may promote the development of novel and more efficacious therapeutic agents.

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2016-01-06
2024-04-18
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Literature Cited

  1. Reiter RJ. 1.  1991. Melatonin: the chemical expression of darkness. Mol. Cell Endocrinol. 79:C153–58 [Google Scholar]
  2. Tosini G, Menaker M. 2.  1996. Circadian rhythms in cultured mammalian retina. Science 272:419–21 [Google Scholar]
  3. Dubocovich ML, Delagrange P, Krause DN, Sugden D, Cardinali DP, Olcese J. 3.  2010. International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors. Pharmacol. Rev. 62:343–80 [Google Scholar]
  4. Foulkes NS, Cassone-Corsi P, Borjigin J, Snyder SH. 4.  1997. Rhythmic transcription: the molecular basis of circadian melatonin synthesis. Trends Neurosci. 20:487–92 [Google Scholar]
  5. Reppert SM, Weaver DR, Godson C. 5.  1996. Melatonin receptors step into the light: cloning and classification of subtypes. Trends Pharmacol. Sci. 17:100–2 [Google Scholar]
  6. Dubocovich ML, Masana MI, Iacob S, Sauri DM. 6.  1997. Melatonin receptor antagonists that differentiate between the human Mel1a and Mel1b recombinant subtypes are used to assess the pharmacological profile of the rabbit retina ML1 presynaptic heteroreceptor. Naunyn-Schmiedeberg's Arch. Pharmacol. 355:365–75 [Google Scholar]
  7. Audinot V, Mailliet F, Lahaye-Brasseur C, Bonnaud A, Le Gall A. 7.  et al. 2003. New selective ligands of human cloned melatonin MT1 and MT2 receptors. Naunyn-Schmiedeberg's Arch. Pharmacol. 367:553–61 [Google Scholar]
  8. Slaugenhaupt SA, Roca AL, Liebert CB, Altherr MR, Gusella JF, Reppert SM. 8.  1995. Mapping of the gene for the Mel1a-melatonin receptor to human chromosome 4 (MTNR1A) and mouse chromosome 8 (Mtnr1a). Genomics 27:355–57 [Google Scholar]
  9. Liu C, Weaver DR, Jin X, Shearman LP, Pieschl RL. 9.  et al. 1997. Molecular dissection of two distinct actions of melatonin on the suprachiasmatic circadian clock. Neuron 19:91–102 [Google Scholar]
  10. Al-Ghoul WM, Herman MD, Dubocovich ML. 10.  1998. Melatonin receptor subtype expression in human cerebellum. NeuroReport 9:4063–68 [Google Scholar]
  11. Weaver DR, Rivkees SA, Reppert SM. 11.  1989. Localization and characterization of melatonin receptors in rodent brain by in vitro autoradiography. J. Neurosci. 9:2581–90 [Google Scholar]
  12. Mazzucchelli C, Pannacci M, Nonno R, Lucini V, Fraschini F, Stankov BM. 12.  1996. The melatonin receptor in the human brain: cloning experiments and distribution studies. Mol. Brain Res. 39:117–26 [Google Scholar]
  13. Adamah-Biassi EB, Zhang Y, Jung H, Vissapragada S, Miller RJ, Dubocovich ML. 13.  2014. Distribution of MT1 melatonin receptor promoter-driven RFP expression in the brains of BAC C3H/HeN transgenic mice. J. Histochem. Cytochem. 62:70–84 [Google Scholar]
  14. Jin X, von Gall C, Pieschl RL, Gribkoff VK, Stehle JH. 14.  et al. 2003. Targeted disruption of the mouse Mel1b melatonin receptor. Mol. Cell. Biol. 23:1054–60 [Google Scholar]
  15. Dubocovich ML. 15.  1988. Luzindole (N-0774): a novel melatonin receptor antagonist. J. Pharmacol. Exp. Ther. 246:902–10 [Google Scholar]
  16. Dubocovich ML. 16.  1993. Melatonin receptor agonists and antagonists. Trends in Drug Research V Claassen 285–91 Amsterdam: Elsevier [Google Scholar]
  17. Dubocovich ML, Yun K, Al-Ghoul WM, Benloucif S, Masana MI. 17.  1998. Selective MT2 melatonin receptor antagonists block melatonin-mediated phase advances of circadian rhythms. FASEB J. 12:1211–20 [Google Scholar]
  18. Dubocovich ML, Masana M. 18.  1998. The efficacy of melatonin receptor analogues is dependent on the level of human melatonin receptor subtype expression. Biological Clocks, Mechanisms and Applications Y Touitou 289–93 Amsterdam: Elsevier [Google Scholar]
  19. Browning C, Beresford I, Fraser N, Giles H. 19.  2000. Pharmacological characterization of human recombinant melatonin mt1 and MT2 receptors. Br. J. Pharmacol. 129:877–86 [Google Scholar]
  20. Sugden D, Yeh LK, Teh MT. 20.  1999. Design of subtype selective melatonin receptor agonists and antagonists. Reprod. Nutr. Dev. 39:335–44 [Google Scholar]
  21. Baba K, Benleulmi-Chaachoua A, Journe AS, Kamal M, Guillaume JL. 21.  et al. 2013. Heteromeric MT1/MT2 melatonin receptors modulate photoreceptor function. Sci. Signal. 6:ra89 [Google Scholar]
  22. Rivara S, Pala D, Lodola A, Mor M, Lucini V. 22.  et al. 2012. MT1-selective melatonin receptor ligands: synthesis, pharmacological evaluation, and molecular dynamics investigation of N-{[(3-O-Substituted)anilino]alkyl}amides. ChemMedChem 7:1954–64 [Google Scholar]
  23. Descamps-François C, Yous S, Chavatte P, Audinot V, Bonnaud A. 23.  et al. 2003. Design and synthesis of naphthalenic dimers as selective MT1 melatoninergic ligands. J. Med. Chem. 46:1127–29 [Google Scholar]
  24. Kenakin TP. 24.  2014. Orthosteric drug antagonism. A Pharmacology Primer: Techniques for More Effective and Strategic Drug Discovery TP Kenakin 119–53 New York: Academic [Google Scholar]
  25. Urban JD, Clarke WP, von Zastrow M, Nichols DE, Kobilka B. 25.  et al. 2007. Functional selectivity and classical concepts of quantitative pharmacology. J. Pharmacol. Exp. Ther. 320:1–13 [Google Scholar]
  26. Audinot V, Bonnaud A, Grandcolas L, Rodriguez M, Nagel N. 26.  et al. 2008. Molecular cloning and pharmacological characterization of rat melatonin MT1 and MT2 receptors. Biochem. Pharmacol. 75:2007–19 [Google Scholar]
  27. Cogé F, Guenin SP, Fery I, Migaud M, Devavry S. 27.  et al. 2009. The end of a myth: cloning and characterization of the ovine melatonin MT2 receptor. Brit. J. Pharmacol. 158:1248–62 [Google Scholar]
  28. Mailliet F, Audinot V, Malpaux B, Bonnaud A, Delagrange P. 28.  et al. 2004. Molecular pharmacology of the ovine melatonin receptor: comparison with recombinant human MT1 and MT2 receptors. Biochem. Pharmacol. 67:667–77 [Google Scholar]
  29. Doolen S, Krause DN, Dubocovich ML, Duckles SP. 29.  1998. Melatonin mediates two distinct responses in vascular smooth muscle. Eur. J. Pharmacol. 345:67–69 [Google Scholar]
  30. Ochoa-Sanchez R, Comai S, Lacoste B, Bambico FR, Dominguez-Lopez S. 30.  et al. 2011. Promotion of non-rapid eye movement sleep and activation of reticular thalamic neurons by a novel MT2 melatonin receptor ligand. J. Neurosci. 31:18439–52 [Google Scholar]
  31. Wan Q, Man H-Y, Liu F, Braunton J, Niznik HB. 31.  et al. 1999. Differential modulation of GABAA receptor function by Mel1a and Mel1b receptors. Nat. Neurosci. 2:401–3 [Google Scholar]
  32. Ayoub MA, Levoye A, Delagrange P, Jockers R. 32.  2004. Preferential formation of MT1/MT2 melatonin receptor heterodimers with distinct ligand interaction properties compared with MT2 homodimers. Mol. Pharmacol. 66:312–21 [Google Scholar]
  33. Gerdin MJ, Masana MI, Dubocovich ML. 33.  2004. Melatonin-mediated regulation of human MT1 melatonin receptors expressed in mammalian cells. Biochem. Pharmacol. 67:2023–30 [Google Scholar]
  34. Gerdin MJ, Masana MI, Rivera-Bermúdez MA, Hudson RL, Earnest DJ. 34.  et al. 2004. Melatonin desensitizes endogenous MT2 melatonin receptors in the rat suprachiasmatic nucleus: relevance for defining the periods of sensitivity of the mammalian circadian clock to melatonin. FASEB J. 18:1646–56 [Google Scholar]
  35. Kokkola T, Vaittinen M, Laitinen JT. 35.  2007. Inverse agonist exposure enhances ligand binding and G protein activation of the human MT1 melatonin receptor, but leads to receptor down-regulation. J. Pineal Res. 43:255–62 [Google Scholar]
  36. Kamal M, Gbahou F, Guillaume JL, Daulat AM, Benleulmi-Chaachoua A. 36.  et al. 2015. Convergence of melatonin and serotonin (5-HT) signaling at MT2/5-HT2C receptor heteromers. J. Biol. Chem. 290:11537–46 [Google Scholar]
  37. de Bodinat C, Guardiola-Lemaitre B, Mocaër E, Renard P, Muñoz C, Millan MJ. 37.  2010. Agomelatine, the first melatonergic antidepressant: discovery, characterization and development. Nat. Rev. Drug Discov. 9:628–42 [Google Scholar]
  38. Paulis L, Simko F, Laudon M. 38.  2012. Cardiovascular effects of melatonin receptor agonists. Expert Opin. Investig. Drugs 21:1661–78 [Google Scholar]
  39. Mini LJ, Wang-Weigand S, Zhang J. 39.  2007. Self-reported efficacy and tolerability of ramelteon 8 mg in older adults experiencing severe sleep-onset difficulty. Am. J. Geriatr. Pharmacother. 5:177–84 [Google Scholar]
  40. Rajaratnam SMW, Polymeropoulos MH, Fisher DM, Roth T, Scott C. 40.  et al. 2009. Melatonin agonist tasimelteon (VEC-162) for transient insomnia after sleep-time shift: two randomised controlled multicentre trials. Lancet 373:482–91 [Google Scholar]
  41. Lavedan C, Forsberg M, Gentile AJ. 41.  2015. Tasimelteon: a selective and unique receptor binding profile. Neuropharmacology 91:142–47 [Google Scholar]
  42. Kato K, Hirai K, Nishiyama K, Uchikawa O, Fukatsu K. 42.  et al. 2005. Neurochemical properties of ramelteon (TAK-375), a selective MT1/MT2 receptor agonist. Neuropharmacology 48:301–10 [Google Scholar]
  43. Millan MJ, Gobert A, Lejeune F, Dekeyne A, Newman-Tancredi A. 43.  et al. 2003. The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxytryptamine2c receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways. J. Pharmacol. Exp. Ther. 306:954–64 [Google Scholar]
  44. Ying S-W, Rusak B, Delagrange P, Mocaër E, Renard P, Guardiola-Lemaître B. 44.  1996. Melatonin analogues as agonists and antagonists in the circadian system and other brain areas. Eur. J. Pharmacol. 296:33–42 [Google Scholar]
  45. Boutin JA, Audinot V, Ferry G, Delagrange P. 45.  2005. Molecular tools to study melatonin pathways and actions. Trends Pharmacol. Sci. 26:412–19 [Google Scholar]
  46. Nishiyama K, Nishikawa H, Kato K, Miyamoto M, Tsukamoto T, Hirai K. 46.  2014. Pharmacological characterization of M-II, the major human metabolite of ramelteon. Pharmacology 93:197–201 [Google Scholar]
  47. Arendt J, Skene DJ. 47.  2005. Melatonin as a chronobiotic. Sleep Med. Rev. 9:25–39 [Google Scholar]
  48. Cajochen C, Kräuchi K, von Arx MA, Möri D, Graw P, Wirz-Justice A. 48.  1996. Daytime melatonin administration enhances sleepiness and theta/alpha activity in the waking EEG. Neurosci. Lett. 207:209–13 [Google Scholar]
  49. Zhdanova IV. 49.  2005. Melatonin as a hypnotic: pro. Sleep Med. Rev. 9:51–65 [Google Scholar]
  50. Lewy AJ, Ahmed S, Jackson JML, Sack RL. 50.  1992. Melatonin shifts human circadian-rhythms according to a phase response curve. Chronobiol. Int. 9:380–92 [Google Scholar]
  51. Burgess HJ, Revell VL, Molina TA, Eastman CI. 51.  2010. Human phase response curves to three days of daily melatonin: 0.5 mg versus 3.0 mg. J. Clin. Endocr. Metab. 95:3325–31 [Google Scholar]
  52. Lewy AJ, Emens JS, Lefler BJ, Yuhas K, Jackman AR. 52.  2005. Melatonin entrains free-running blind people according to a physiological dose-response curve. Chronobiol. Int. 22:1093–106 [Google Scholar]
  53. Lewy AJ, Bauer VK, Cutler NL, Sack RL. 53.  1998. Melatonin treatment of winter depression: a pilot study. Psychiat. Res. 77:57–61 [Google Scholar]
  54. Roth T, Roehrs T. 54.  2003. Insomnia: epidemiology, characteristics, and consequences. Clin. Cornerstone 5:5–15 [Google Scholar]
  55. Roth T. 55.  2007. Insomnia: definition, prevalence, etiology, and consequences. J. Clin. Sleep Med. 3:S7–10 [Google Scholar]
  56. Laudon M, Frydman-Marom A. 56.  2014. Therapeutic effects of melatonin receptor agonists on sleep and comorbid disorders. Int. J. Mol. Sci. 15:15924–50 [Google Scholar]
  57. Zhu L, Zee PC. 57.  2012. Circadian rhythm sleep disorders. Neurol. Clin. 30:1167–91 [Google Scholar]
  58. Mundey K, Benloucif S, Harsanyi K, Dubocovich ML, Zee PC. 58.  2005. Phase-dependent treatment of delayed sleep phase syndrome with melatonin. Sleep 28:1271–78 [Google Scholar]
  59. Hunt AE, Al-Ghoul WM, Gillette MU, Dubocovich ML. 59.  2001. Activation of MT2 melatonin receptors in rat suprachiasmatic nucleus phase advances the circadian clock. Am. J. Physiol. Cell Physiol. 280:C110–18 [Google Scholar]
  60. Dubocovich ML. 60.  2007. Melatonin receptors: role on sleep and circadian rhythm regulation. Sleep Med. 8:Suppl. 334–42 [Google Scholar]
  61. Benloucif S, Dubocovich ML. 61.  1996. Melatonin and light induce phase shifts of circadian activity rhythms in the C3H/HeN mouse. J. Biol. Rhythms 11:113–25 [Google Scholar]
  62. Rawashdeh O, Hudson RL, Stepien I, Dubocovich ML. 62.  2011. Circadian periods of sensitivity for ramelteon on the onset of running-wheel activity and the peak of suprachiasmatic nucleus neuronal firing rhythms in C3H/HeN mice. Chronobiol. Int. 28:31–38 [Google Scholar]
  63. Dubocovich M, Hudson RL, Smith MR. 63.  2007. Use of mice with genetic deletion of MT1 and/or MT2 receptors to unravel the receptor type mediating phase shift of circadian rhythms by ramelteon Presented at Annu. Conf. Am. Coll. Neuropsychopharmacol. (ACNP) Session II 177, Dec. 9–13, Boca Raton, FL
  64. Dubocovich ML, Hudson RL, Sumaya IC, Masana MI, Manna E. 64.  2005. Effect of MT1 melatonin receptor deletion on melatonin-mediated phase shift of circadian rhythms in the C57BL/6 mouse. J. Pineal Res. 39:113–20 [Google Scholar]
  65. Garfinkel D, Laudon M, Nof D, Zisapel N. 65.  1995. Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet 346:541–44 [Google Scholar]
  66. Leger D, Laudon M, Zisapel N. 66.  2004. Nocturnal 6-sulfatoxymelatonin excretion in insomnia and its relation to the response to melatonin replacement therapy. Am. J. Med. 116:91–95 [Google Scholar]
  67. De Leersnyder H, Zisapel N, Laudon M. 67.  2011. Prolonged-release melatonin for children with neurodevelopmental disorders. Pediatr. Neurol 45:23–26 [Google Scholar]
  68. Roth T, Nir T, Zisapel N. 68.  2015. Prolonged release melatonin for improving sleep in totally blind subjects: a pilot placebo-controlled multicenter trial. Nat. Sci. Sleep 7:13–23 [Google Scholar]
  69. Miyamoto M, Nishikawa H, Doken Y, Hirai K, Uchikawa O, Ohkawa S. 69.  2004. The sleep-promoting action of ramelteon (TAK-375) in freely moving cats. Sleep 27:1319–25 [Google Scholar]
  70. Yukuhiro N, Kimura H, Nishikawa H, Ohkawa S, Yoshikubo S, Miyamoto M. 70.  2004. Effects of ramelteon (TAK-375) on nocturnal sleep in freely moving monkeys. Brain Res. 102759–66
  71. Roth T, Stubbs C, Walsh JK. 71.  2005. Ramelteon (TAK-375), a selective MT1/MT2-receptor agonist, reduces latency to persistent sleep in a model of transient insomnia related to a novel sleep environment. Sleep 28:303–7 [Google Scholar]
  72. Richardson GS, Zee PC, Wang-Weigand S, Rodriguez L, Peng X. 72.  2008. Circadian phase-shifting effects of repeated ramelteon administration in healthy adults. J. Clin. Sleep Med. 4:456–61 [Google Scholar]
  73. Hirai K, Kita M, Ohta H, Nishikawa H, Fujiwara Y. 73.  et al. 2005. Ramelteon (TAK-375) accelerates reentrainment of circadian rhythm after a phase advance of the light-dark cycle in rats. J. Biol. Rhythms 20:27–37 [Google Scholar]
  74. Stahl SM. 74.  2014. Mechanism of action of tasimelteon in non-24 sleep-wake syndrome: treatment for a circadian rhythm disorder in blind patients. CNS Spectrums 19:475–78 [Google Scholar]
  75. Mattson RJ, Catt JD, Keavy D, Sloan CP, Epperson J. 75.  et al. 2003. Indanyl piperazines as melatonergic MT2 selective agents. Bioorg. Med. Chem. Lett. 13:1199–202 [Google Scholar]
  76. Fisher SP, Sugden D. 76.  2009. Sleep-promoting action of IIK7, a selective MT2 melatonin receptor agonist in the rat. Neurosci. Lett. 457:93–96 [Google Scholar]
  77. Comai S, Ochoa-Sanchez R, Gobbi G. 77.  2013. Sleep-wake characterization of double MT1/MT2 receptor knockout mice and comparison with MT1 and MT2 receptor knockout mice. Behav. Brain Res. 243:231–38 [Google Scholar]
  78. Murray CJL, Lopez AD. 78.  1997. Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study. Lancet 349:1498–504 [Google Scholar]
  79. Williams JW, Mulrow CD, Chiquette E, Noel PH, Aguilar C, Cornell J. 79.  2000. A systematic review of newer pharmacotherapies for depression in adults: evidence report summary. Ann. Intern. Med. 132:743–56 [Google Scholar]
  80. Anderson IM, Tomenson BM. 80.  1995. Treatment discontinuation with selective serotonin reuptake inhibitors compared with tricyclic antidepressants: a metaanalysis. Br. Med. J. 310:1433–38 [Google Scholar]
  81. Micale V, Arezzi A, Rampello L, Drago F. 81.  2006. Melatonin affects the immobility time of rats in the forced swim test: the role of serotonin neurotransmission. Eur. Neuropsychopharm. 16:538–45 [Google Scholar]
  82. Overstreet DH, Pucilowski O, Retton MC, Delagrange P, Guardiola-Lemaitre B. 82.  1998. Effects of melatonin receptor ligands on swim test immobility. NeuroReport 9:249–53 [Google Scholar]
  83. Liu JB, Somera-Molina KC, Hudson RL, Dubocovich ML. 83.  2013. Melatonin potentiates running wheel-induced neurogenesis in the dentate gyrus of adult C3H/HeN mice hippocampus. J. Pineal. Res. 54:222–31 [Google Scholar]
  84. Ramírez-Rodriguez G, Ortiz-López L, Dominguez-Alonso A, Benítez-King GA, Kempermann G. 84.  2011. Chronic treatment with melatonin stimulates dendrite maturation and complexity in adult hippocampal neurogenesis of mice. J. Pineal Res. 50:29–37 [Google Scholar]
  85. Ramírez-Rodriguez G, Klempin F, Babu H, Benítez-King G, Kempermann G. 85.  2009. Melatonin modulates cell survival of new neurons in the hippocampus of adult mice. Neuropsychopharmacology 34:2180–91 [Google Scholar]
  86. Weil ZM, Hotchkiss AK, Gatien ML, Pieke-Dahl S, Nelson RJ. 86.  2006. Melatonin receptor (MT1) knockout mice display depression-like behaviors and deficits in sensorimotor gating. Brain Res. Bull. 68:425–29 [Google Scholar]
  87. Adamah-Biassi EB, Hudson RL, Dubocovich ML. 87.  2014. Genetic deletion of MT1 melatonin receptors alters spontaneous behavioral rhythms in male and female C57BL/6 mice. Hormones Behav. 66:619–27 [Google Scholar]
  88. Wu Y-H, Ursinus J, Zhou J-N, Scheer FAJL, Bao A-M. 88.  et al. 2013. Alterations of melatonin receptors MT1 and MT2 in the hypothalamic suprachiasmatic nucleus during depression. J. Affect. Disord. 148:357–67 [Google Scholar]
  89. Hansen MV, Danielsen AK, Hageman I, Rosenberg J, Gogenur I. 89.  2014. The therapeutic or prophylactic effect of exogenous melatonin against depression and depressive symptoms: a systematic review and meta-analysis. Eur. Neuropsychopharm. 24:1719–28 [Google Scholar]
  90. Hickie IB, Rogers NL. 90.  2011. Novel melatonin-based therapies: potential advances in the treatment of major depression. Lancet 378:621–31 [Google Scholar]
  91. Bertaina-Anglade V, Drieu la Rochelle C, Boyer P-A, Mocaër E. 91.  2006. Antidepressant-like effects of agomelatine (S 20098) in the learned helplessness model. Behav. Pharmacol. 17:703–13 [Google Scholar]
  92. Banasr M, Soumier A, Hery M, Mocaër E, Daszuta A. 92.  2006. Agomelatine, a new antidepressant, induces regional changes in hippocampal neurogenesis. Biol. Psychiatry 59:1087–96 [Google Scholar]
  93. Soumier A, Banasr M, Lortet S, Masmejean F, Bernard N. 93.  et al. 2009. Mechanisms contributing to the phase-dependent regulation of neurogenesis by the novel antidepressant, agomelatine, in the adult rat hippocampus. Neuropsychopharmacology 34:2390–403 [Google Scholar]
  94. Schmelting B, Corbach-Soehle S, Kohlhause S, Schlumbohm C, Fluegge G, Fuchs E. 94.  2014. Agomelatine in the tree shrew model of depression: effects on stress-induced nocturnal hyperthermia and hormonal status. Eur. Neuropsychopharm. 24:437–47 [Google Scholar]
  95. Dubocovich ML, Mogilnicka E, Areso PM. 95.  1990. Antidepressant-like activity of the melatonin receptor antagonist, luzindole (N-0774), in the mouse behavioral despair test. Eur. J. Pharmacol. 182:313–25 [Google Scholar]
  96. Sumaya IC, Masana MI, Dubocovich ML. 96.  2005. The antidepressant-like effect of the melatonin receptor ligand luzindole in mice during forced swimming requires expression of MT2 but not MT1 melatonin receptors. J. Pineal Res. 39:170–77 [Google Scholar]
  97. Dubocovich ML, Sumaya IC, Zelivyanskaya ML, Soto C, Stepien I. 97.  2006. Antidepressant-like effect in the swimming test and increased cell proliferation/survival in hippocampus of adult C3H/HeN mice chronically treated with the melatonin (MLT) receptor ligand luzindole. Neuropsychopharmacology 31:S172 [Google Scholar]
  98. Souêtre E, Salvati E, Belugou JL, Pringuey D, Candito M. 98.  et al. 1989. Circadian-rhythms in depression and recovery: evidence for blunted amplitude as the main chronobiological abnormality. Psychiat. Res. 28:263–78 [Google Scholar]
  99. Kräuchi K, Cajochen C, Möri D, Graw P, Wirz-Justice A. 99.  1997. Early evening melatonin and S-20098 advance circadian phase and nocturnal regulation of core body temperature. Am. J. Physiol. 272:R1178–88 [Google Scholar]
  100. Leproult R, Van Onderbergen A, L'Hermite-Balériaux M, Van Cauter E, Copinschi G. 100.  2005. Phase-shifts of 24-h rhythms of hormonal release and body temperature following early evening administration of the melatonin agonist agomelatine in healthy older men. Clin. Endocrinol. 63:298–304 [Google Scholar]
  101. Lemoine P, Guilleminault C, Alvarez E. 101.  2007. Improvement in subjective sleep in major depressive disorder with a novel antidepressant, agomelatine: randomized, double-blind comparison with venlafaxine. J. Clin. Psychiatry 68:1723–32 [Google Scholar]
  102. Duman RS, Monteggia LM. 102.  2006. A neurotrophic model for stress-related mood disorders. Biol. Psychiatry 59:1116–27 [Google Scholar]
  103. Kempermann G, Wiskott L, Gage FH. 103.  2004. Functional significance of adult neurogenesis. Curr. Opin. Neurobiol. 14:186–91 [Google Scholar]
  104. Racagni G, Riva MA, Molteni R, Musazzi L, Calabrese F. 104.  et al. 2011. Mode of action of agomelatine: synergy between melatonergic and 5-HT2C receptors. World J. Biol. Psychiatry 12:574–87 [Google Scholar]
  105. Thies W, Bleiler L. 105.  2012. 2012 Alzheimer's disease facts and figures. Alzheimer's Dement. 8:131–68 [Google Scholar]
  106. Savaskan E, Ayoub MA, Ravid R, Angeloni D, Fraschini F. 106.  et al. 2005. Reduced hippocampal MT2 melatonin receptor expression in Alzheimer's disease. J. Pineal Res. 38:10–16 [Google Scholar]
  107. Savaskan E, Olivieri G, Meier F, Brydon L, Jockers R. 107.  et al. 2002. Increased melatonin 1a-receptor immunoreactivity in the hippocampus of Alzheimer's disease patients. J. Pineal Res. 32:59–62 [Google Scholar]
  108. Cooke SF, Bliss TVP. 108.  2006. Plasticity in the human central nervous system. Brain 129:1659–73 [Google Scholar]
  109. Bliss TVP, Collingridge GL. 109.  1993. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39 [Google Scholar]
  110. Wang LM, Suthana NA, Chaudhury D, Weaver DR, Colwell CS. 110.  2005. Melatonin inhibits hippocampal long-term potentiation. Eur. J. Neurosci. 22:2231–37 [Google Scholar]
  111. Larson J, Jessen RE, Uz T, Arslan AD, Kurtuncu M. 111.  et al. 2006. Impaired hippocampal long-term potentiation in melatonin MT2 receptor-deficient mice. Neurosci. Lett. 393:23–26 [Google Scholar]
  112. Rawashdeh O, de Borsetti NH, Roman G, Cahill GM. 112.  2007. Melatonin suppresses nighttime memory formation in zebrafish. Science 318:1144–46 [Google Scholar]
  113. O'Neal-Moffitt G, Pilli J, Kumar SS, Olcese J. 113.  2014. Genetic deletion of MT1/MT2 melatonin receptors enhances murine cognitive and motor performance. Neuroscience 277:506–21 [Google Scholar]
  114. Gorfine T, Zisapel N. 114.  2007. Melatonin and the human hippocampus, a time dependent interplay. J. Pineal Res. 43:80–86 [Google Scholar]
  115. Tan DX, Manchester LC, Sainz RM, Mayo JC, Leon J, Reiter RJ. 115.  2005. Physiological ischemia/reperfusion phenomena and their relation to endogenous melatonin production: a hypothesis. Endocrine 27:149–58 [Google Scholar]
  116. Galano A, Tan DX, Reiter RJ. 116.  2013. On the free radical scavenging activities of melatonin's metabolites, AFMK and AMK. J. Pineal Res. 54:245–57 [Google Scholar]
  117. Parada E, Buendia I, León R, Negredo P, Romero A. 117.  et al. 2014. Neuroprotective effect of melatonin against ischemia is partially mediated by alpha-7 nicotinic receptor modulation and HO-1 overexpression. J. Pineal Res. 56:204–12 [Google Scholar]
  118. Wang X, Sirianni A, Pei Z, Cormier K, Smith K. 118.  et al. 2011. The melatonin MT1 receptor axis modulates mutant huntingtin-mediated toxicity. J. Neurosci. 31:14496–507 [Google Scholar]
  119. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ. 119.  et al. 2014. Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation 131:e29–322 [Google Scholar]
  120. Lee CH, Yoo K-Y, Choi JH, Park OK, Hwang IK. 120.  et al. 2010. Melatonin's protective action against ischemic neuronal damage is associated with up-regulation of the MT2 melatonin receptor. J. Neurosci. Res. 88:2630–40 [Google Scholar]
  121. Chern C-M, Liao J-F, Wang Y-H, Shen Y-C. 121.  2012. Melatonin ameliorates neural function by promoting endogenous neurogenesis through the MT2 melatonin receptor in ischemic-stroke mice. Free Radic. Biol. Med. 52:1634–47 [Google Scholar]
  122. 122. Subst. Abus. Ment. Health Serv. Adm 2013. Results of the 2012 national survey on drug use and health: summary of national findings. NSDUH Series H-46, HHS Publ. No. (SMA) 13–4795, US Dep. Health Hum. Serv., Rockville, MD. http://www.samhsa.gov/data/sites/default/files/NSDUHresults2012/NSDUHresults2012.pdf
  123. 123. Natl. Inst. Drug Abus 2007. Drugs, brains, and behavior: the science of addiction. Natl. Inst. Health Publ. No. 14-5605, Bethesda, MD. http://www.drugabuse.gov/sites/default/files/soa_2014.pdf
  124. Hutchinson AJ, Hudson RL, Dubocovich ML. 124.  2012. Genetic deletion of MT1 and MT2 melatonin receptors differentially abrogates the development and expression of methamphetamine-induced locomotor sensitization during the day and the night in C3H/HeN mice. J. Pineal Res. 53:399–409 [Google Scholar]
  125. Hutchinson AJ, Ma J, Liu J, Hudson RL, Dubocovich ML. 125.  2014. Role of MT1 melatonin receptors in methamphetamine-induced locomotor sensitization in C57BL/6 mice. Psychopharmacology 231:257–67 [Google Scholar]
  126. Clough SJ, Hutchinson AJ, Hudson RL, Dubocovich ML. 126.  2014. Genetic deletion of the MT1 or MT2 melatonin receptors abrogates methamphetamine-induced reward in C3H/HeN mice. Physiol. Behav. 132:79–86 [Google Scholar]
  127. Uz T, Javaid JI, Manev H. 127.  2002. Circadian differences in behavioral sensitization to cocaine: putative role of arylalkylamine N-acetyltransferase. Life Sci. 70:3069–75 [Google Scholar]
  128. Kurtuncu M, Arslan AD, Akhisaroglu M, Manev H, Uz T. 128.  2004. Involvement of the pineal gland in diurnal cocaine reward in mice. Eur. J. Pharmacol. 489:203–5 [Google Scholar]
  129. Robinson TE, Berridge KC. 129.  2000. The psychology and neurobiology of addiction: an incentive-sensitization view. Addiction 95:Suppl. 2S91–117 [Google Scholar]
  130. Masana MI, Benloucif S, Dubocovich ML. 130.  2000. Circadian rhythm of mt1 melatonin receptor expression in the suprachiasmatic nucleus of the C3H/HeN mouse. J. Pineal Res. 28:185–92 [Google Scholar]
  131. Roseboom PH, Namboodiri MAA, Zimonjic DB, Popescu NC, Rodriguez IR. 131.  et al. 1998. Natural melatonin ‘knockdown’ in C57BL/6J mice: rare mechanism truncates serotonin N-acetyltransferase. Brain Res. Mol. Brain Res. 63:189–97 [Google Scholar]
  132. Han J, Xu Y, Yu C-X, Shen J, Wei Y-M. 132.  2008. Melatonin reverses the expression of morphine-induced conditioned place preference through its receptors within central nervous system in mice. Eur. J. Pharmacol. 594:125–31 [Google Scholar]
  133. Witt-Enderby PA, Radio NM, Doctor JS, Davis VL. 133.  2006. Therapeutic treatments potentially mediated by melatonin receptors: potential clinical uses in the prevention of osteoporosis, cancer and as an adjuvant therapy. J. Pineal Res. 41:297–305 [Google Scholar]
  134. Lissoni P, Barni S, Mandala M, Ardizzoia A, Paolorossi F. 134.  et al. 1999. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur. J. Cancer 35:1688–92 [Google Scholar]
  135. Lissoni P, Barni S, Meregalli S, Fossati V, Cazzaniga M. 135.  et al. 1995. Modulation of cancer endocrine therapy by melatonin: a Phase II study of tamoxifen plus melatonin in metastatic breast-cancer patients progressing under tamoxifen alone. Brit. J. Cancer 71:854–56 [Google Scholar]
  136. Jemal A, Thomas A, Murray T, Thun M. 136.  2002. Cancer statistics, 2002. CA Cancer J. Clin. 52:23–47 [Google Scholar]
  137. Lissoni P, Ardizzoia A, Barni S, Paolorossi F, Tancini G. 137.  et al. 1995. A randomized study of tamoxifen alone versus tamoxifen plus melatonin in estrogen receptor-negative heavily pretreated metastatic breast-cancer patients. Oncol. Rep. 2:871–73 [Google Scholar]
  138. Davis S, Mirick DK, Stevens RG. 138.  2001. Night shift work, light at night, and risk of breast cancer. J. Natl. Cancer Inst. 93:1557–62 [Google Scholar]
  139. Shah PN, Mhatre MC, Kothari LS. 139.  1984. Effect of melatonin on mammary carcinogenesis in intact and pinealectomized rats in varying photoperiods. Cancer Res. 44:3403–7 [Google Scholar]
  140. Blask DE, Brainard GC, Dauchy RT, Hanifin JP, Davidson LK. 140.  et al. 2005. Melatonin-depleted blood from premenopausal women exposed to light at night stimulates growth of human breast cancer xenografts in nude rats. Cancer Res. 65:11174–84 [Google Scholar]
  141. Blask DE, Sauer LA, Dauchy RT, Holowachuk EW, Ruhoff MS, Kopff HS. 141.  1999. Melatonin inhibition of cancer growth in vivo involves suppression of tumor fatty acid metabolism via melatonin receptor-mediated signal transduction events. Cancer Res. 59:4693–701 [Google Scholar]
  142. Ram PT, Dai J, Yuan L, Dong C, Kiefer TL. 142.  et al. 2002. Involvement of the mt1 melatonin receptor in human breast cancer. Cancer Lett. 179:141–50 [Google Scholar]
  143. Lai L, Yuan L, Cheng Q, Dong CM, Mao LL, Hill SM. 143.  2009. Alteration of the MT1 melatonin receptor gene and its expression in primary human breast tumors and breast cancer cell lines. Breast Cancer Res. Treat. 118:293–305 [Google Scholar]
  144. Rögelsperger O, Ekmekcioglu C, Jäger W, Klimpfinger M, Königsberg R. 144.  et al. 2009. Coexpression of the melatonin receptor 1 and nestin in human breast cancer specimens. J. Pineal Res. 46:422–32 [Google Scholar]
  145. Yuan L, Collins AR, Dai J, Dubocovich ML, Hill SM. 145.  2002. MT1 melatonin receptor overexpression enhances the growth suppressive effect of melatonin in human breast cancer cells. Mol. Cell Endocrinol. 192:147–56 [Google Scholar]
  146. Collins A, Yuan L, Kiefer TL, Cheng Q, Lai L, Hill SM. 146.  2003. Overexpression of the MT1 melatonin receptor in MCF-7 human breast cancer cells inhibits mammary tumor formation in nude mice. Cancer Lett. 189:49–57 [Google Scholar]
  147. Xi SC, Tam PC, Brown GM, Pang SF, Shiu SYW. 147.  2000. Potential involvement of mt1 receptor and attenuated sex steroid-induced calcium influx in the direct anti-proliferative action of melatonin on androgen-responsive LNCaP human prostate cancer cells. J. Pineal Res. 29:172–83 [Google Scholar]
  148. Xi SC, Siu SWF, Fong SW, Shiu SYW. 148.  2001. Inhibition of androgen-sensitive LNCaP prostate cancer growth in vivo by melatonin: association of antiproliferative action of the pineal hormone with mt1 receptor protein expression. Prostate 46:52–61 [Google Scholar]
  149. Shiu SYW, Law IC, Lau KW, Tam PC, Yip AWC, Ng WT. 149.  2003. Melatonin slowed the early biochemical progression of hormone-refractory prostate cancer in a patient whose prostate tumor tissue expressed MT1 receptor subtype. J. Pineal Res. 35:177–82 [Google Scholar]
  150. Tam CW, Mo CW, Yao K-M, Shiu SYW. 150.  2007. Signaling mechanisms of melatonin in antiproliferation of hormone-refractory 22Rv1 human prostate cancer cells: implications for prostate cancer chemoprevention. J. Pineal Res. 42:191–202 [Google Scholar]
  151. Clough SJ, Hutchinson AJ, Dubocovich ML. 151.  2016. Melatonin receptors as modulators of methamphetamine mediated behaviors. The Neuropathology of Drug Addictions and Substance Misuse V Preedy New York: Academic. In press [Google Scholar]
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