Dysfunction of serotonergic activity and emotional responses across the light‐dark cycle in mice lacking melatonin  MT2 receptors. Issue 1 (19th April 2020)

• Record Type: Journal Article
• Authors: Comai, Stefano; De Gregorio, Danilo; Posa, Luca; Ochoa‐Sanchez, Rafael; Bedini, Annalida; Gobbi, Gabriella
• Is Part Of: Journal of pineal research. Volume 69:Issue 1(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-04-19
• Subjects: anxiety -- light/dark cycle -- melatonin -- MT2 receptors -- serotonin -- UCM1014; Pineal gland -- Periodicals; Pineal Gland -- Periodicals; Épiphyse (Glande); Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 612.492
• DOI: 10.1111/jpi.12653
• Languages: English
• ISSNs: 0742-3098

Abstract

Abstract: 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.