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Dysfunction of serotonergic activity and emotional responses across the light-dark cycle in mice lacking melatonin  MT2 receptors.
Comai, Stefano; De Gregorio, Danilo; Posa, Luca; Ochoa-Sanchez, Rafael; Bedini, Annalida; Gobbi, Gabriella.
Afiliación
  • Comai S; Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University and McGill University Health Center, Montreal, QC, Canada.
  • De Gregorio D; Division of Neuroscience, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy.
  • Posa L; Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University and McGill University Health Center, Montreal, QC, Canada.
  • Ochoa-Sanchez R; Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University and McGill University Health Center, Montreal, QC, Canada.
  • Bedini A; Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University and McGill University Health Center, Montreal, QC, Canada.
  • Gobbi G; Department of Biomolecular Sciences, University Carlo Bo, Urbino, Italy.
J Pineal Res ; 69(1): e12653, 2020 Aug.
Article en En | MEDLINE | ID: mdl-32239546
Melatonin (MLT) levels fluctuate according to the external light/dark cycle in both diurnal and nocturnal mammals. We previously demonstrated that melatonin MT2 receptor knockout (MT2 -/- ) mice show a decreased nonrapid eye movement sleep over 24 hours and increased wakefulness during the inactive (light) phase. Here, we investigated the role of MT2 receptors in physiological light/dark cycle fluctuations in the activity of dorsal raphe nucleus (DRN) serotonin (5-HT) neurons and anxiety- and depression-like behavior. We found that the 5-HT burst-firing activity was tonically reduced across the whole 24 hours in MT2 -/- mice compared with MT2 +/+ mice.  Importantly, the physiological changes in the spontaneous firing activity of DRN 5-HT neurons during the light/dark cycle were nullified in MT2 -/- mice, with a higher DRN 5-HT neural firing activity during the light phase in MT2 -/- than in MT2 +/+  mice. The role of MT2 receptors over DRN 5-HT neurons was confirmed by acute pharmacological studies in which the selective MT2 receptors agonist UCM1014 dose dependently inhibited DRN 5-HT activity, mostly during the dark phase. Compared with MT2 +/+ , MT2 -/- mice displayed an anxiety-like phenotype in the novelty-suppressed feeding and in the light/dark box tests; while anxiety levels in the light/dark box test were lower during the dark than during the light phase in MT2 +/+ mice, the opposite was seen in MT2 -/- mice. No differences between MT2 +/+ and MT2 -/- mice were observed for depression-like behavior in the forced swim and in the sucrose preference tests. These results suggest that MT2 receptor genetic inactivation impacts 5-HT neurotransmission and interferes with anxiety levels by perturbing the physiologic light/dark pattern.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sueño REM / Conducta Animal / Serotonina / Ritmo Circadiano / Receptor de Melatonina MT2 / Emociones / Neuronas Serotoninérgicas Límite: Animals Idioma: En Revista: J Pineal Res Asunto de la revista: ENDOCRINOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sueño REM / Conducta Animal / Serotonina / Ritmo Circadiano / Receptor de Melatonina MT2 / Emociones / Neuronas Serotoninérgicas Límite: Animals Idioma: En Revista: J Pineal Res Asunto de la revista: ENDOCRINOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido