title: Genetic deletion of MT1 melatonin receptors alters spontaneous behavioral rhythms in male and female C57BL/6 mice.
abstract: Behaviors vary over the 24h light/dark cycle and these temporal patterns reflect in part modulation by circadian neural circuits and hormones, such as melatonin. The goal of this study was to investigate the involvement of MT1 melatonin receptors in behavioral regulation by comparing male and female C57 wild type (WT) mice with C57 mice with genetic deletion of the MT1 receptor (MT1KO). A comprehensive array of fifteen distinct spontaneous behaviors was recorded continuously in the homecage over multiple days using the HomeCageScan system. Behaviors assessed were activity-like (i.e. come down, hang, jump, walk), exploration-like (i.e. dig, groom, rear up, sniff, stretch), resting-like (i.e. awake, remain low, rest, twitch) and ingestion-like (i.e. drink, eat). Phenotypic array and temporal distribution analysis revealed distinct behavioral rhythms that differed between WT and MT1KO mice. The rhythms were consistent from day to day in males and varied with the estrous cycle in females. We also studied the role of MT1 receptors on depressive and anxiety-like behaviors. Genetic deletion of MT1 receptors increased immobility time in the forced swim test and decreased the number of marbles buried in the marble burying test in both male and female C57 mice. We conclude that MT1 melatonin receptors are involved in neural pathways modulating diurnal rhythms of spontaneous behavior in the homecage as well as pathways regulating depressive and anxiolytic-like behaviors.
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214, USA.
authors.forename: E B
authors.initials: EB
authors.lastname: Adamah-Biassi
authors.affiliation: Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Hudson
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214, USA. Electronic address: mdubo@buffalo.edu.
authors.forename: M L
authors.initials: ML
authors.lastname: Dubocovich
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics; D001522:Behavior, Animal / Q000502:physiology*; D002940:Circadian Rhythm / Q000235:genetics*; D003863:Depression / Q000235:genetics; D005260:Female; D008297:Male; D008550:Melatonin / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009434:Neural Pathways / Q000378:metabolism; D017440:Photoperiod; D044122:Receptor, Melatonin, MT1 / Q000235:genetics*; D044094:Receptors, Melatonin; D013550:Swimming; D014851:Wakefulness / Q000235:genetics
chemical_list: D044122:Receptor, Melatonin, MT1; D044094:Receptors, Melatonin; D008550:Melatonin
keywords: Behavioral rhythms; C57BL/6 mouse; Estrous cycle; Homecage; MT(1) receptor deletion