title: Melancholic-Like behaviors and circadian neurobiological abnormalities in melatonin MT1 receptor knockout mice.
abstract: BACKGROUND
  Melancholic depression, described also as endogenous depression, is a mood disorder with distinctive specific psychopathological features and biological homogeneity, including anhedonia, circadian variation of mood, psychomotor activation, weight loss, diurnal cortisol changes, and sleep disturbances. Although several hypotheses have been proposed, the etiology of this disorder is still unknown.
  
  
  METHODS
  Behavioral, electrophysiological and biochemical approaches were used to characterize the emotional phenotype, serotonergic and noradrenergic electrical activity, and corticosterone in melatonin MT1 receptor knockout mice and their wild type counterparts, during both light and dark phases.
  
  
  RESULTS
  Melatonin MT1 receptor knockout mice have decreased mobility in the forced swim and tail suspension tests as well as decreased sucrose consumption, mostly during the dark/inactive phase. These mood variations are reversed by chronic treatment with the tricyclic antidepressant desipramine. In addition, MT1 receptor knockout mice exhibit psychomotor disturbances, higher serum levels of corticosterone the dark phase, and a blunted circadian variation of corticosterone levels. In vivo electrophysiological recordings show a decreased burst-firing activity of locus coeruleus norepinephrine neurons during the dark phase. The circadian physiological variation in the spontaneous firing activity of high-firing neuronal subpopulations of both norepinephrine neurons and dorsal raphe serotonin neurons are abolished in MT1 knockout mice.
  
  
  CONCLUSIONS
  These data demonstrate that melatonin MT1 receptor knockout mice recapitulate several behavioral and neurobiological circadian changes of human melancholic depression and, for the first time, suggest that the MT1 receptor may be implicated in the pathogenesis of melancholic depression and is a potential pharmacological target for this mental condition.
authors: Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University and McGill University Health Center, Montréal, QC, Canada (Drs Comai, Ochoa-Sanchez, Dominguez-Lopez, Bambico, and Gobbi).
authors: Stefano
authors: S
authors: Comai
authors: Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University and McGill University Health Center, Montréal, QC, Canada (Drs Comai, Ochoa-Sanchez, Dominguez-Lopez, Bambico, and Gobbi).
authors: Rafael
authors: R
authors: Ochoa-Sanchez
authors: Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University and McGill University Health Center, Montréal, QC, Canada (Drs Comai, Ochoa-Sanchez, Dominguez-Lopez, Bambico, and Gobbi).
authors: Sergio
authors: S
authors: Dominguez-Lopez
authors: Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University and McGill University Health Center, Montréal, QC, Canada (Drs Comai, Ochoa-Sanchez, Dominguez-Lopez, Bambico, and Gobbi).
authors: Francis Rodriguez
authors: FR
authors: Bambico
authors: Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University and McGill University Health Center, Montréal, QC, Canada (Drs Comai, Ochoa-Sanchez, Dominguez-Lopez, Bambico, and Gobbi). gabriella.gobbi@mcgill.ca.
authors: Gabriella
authors: G
authors: Gobbi
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D021081:Chronobiology Disorders / Q000188:drug therapy / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics*; D003345:Corticosterone / Q000097:blood; D003866:Depressive Disorder / Q000188:drug therapy / Q000235:genetics*; D003891:Desipramine / Q000627:therapeutic use; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D005518:Food Preferences; D019417:Hindlimb Suspension; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D044122:Receptor, Melatonin, MT1 / Q000172:deficiency* / Q000235:genetics; D013550:Swimming
chemical_list: D000929:Antidepressive Agents, Tricyclic; D044122:Receptor, Melatonin, MT1; D003891:Desipramine; D003345:Corticosterone
keywords: MT1 receptors; circadian rhythm; corticosterone; daily mood variations; melancholic depression; monoamines; norepinephrine; serotonin
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