Genetic deletion of MT1 melatonin receptors alters spontaneous behavioral rhythms in male and female C57BL/6 mice

Abstract

Behaviors vary over the 24 hr. 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 if MT1 melatonin receptors are involved in behavioral regulation by comparing male and female C57 wild type (WT) mice with C57 mice that had a 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.

Melatonin Receptor 1 Deficiency Affects Feeding Dynamics and Pro-Opiomelanocortin<b> </b>Expression in the Arcuate Nucleus and Pituitary of Mice

“…The only significant difference concerned the dynamics of feeding and not the amount of food consumed: MT1-/-mice are 'slow eaters', while the WT mice prefer 'fast food'. This finding is in line with the study of Adamah-Biassi et al [43] showing that melatonin and the MT1 receptor do not have a major influence on the amount of food ingested but affect the temporal dynamics of food intake and various other behaviors. Also the Pomc expression in the PD was found to be under the stimulatory control of the MT1-signaling pathway, because only WT, but not MT1-/-mice, show nocturnal elevated Pomc expression, and exogenous melatonin injected during daytime stimulates Pomc expression in the PD of WT mice but not of MT1-/-mice.…”

Melatonin promotes sleep in mice by inhibiting orexin neurons in the perifornical lateral hypothalamus

“…In contrast to diurnal animals (including humans) which produce melatonin just before sleep onset, nocturnal rodents such as the C57BL/6J mice produce melatonin in the pineal gland especially during the middle of the active (dark) period and at the onset of sleep (light) period and express both melatonin receptors. In fact, C57BL/6J mice have been extensively used to understand the role of melatonin in several behaviors . Moreover, sleep‐wakefulness and orexinergic system is also well characterized and extensively studied in C57BL/6J mice …”

Role of the MT1 and MT2 melatonin receptors in mediating depressive‐ and anxiety‐like behaviors in C3H/HeN mice

“…All animal procedures were approved by the University at Buffalo Institutional Animal Care and Use Committee and adhered to the National Institutes of Health guidelines. Detailed analysis of several behavioral domains in the home cage using a 24-h automated video analysis system found no differences between the WT, MT 1 KO and MT 2 KO mice in exploratory, locomotor, ingestive or sleep-related behaviors (Adamah-Biassi et al 2014;Dubocovich laboratory, unpublished data). C3H/HeN mice were bred and maintained in the Laboratory Animal Facility at the University at Buffalo.…”