Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
J Psychopharmacol. 2021 Oct;35(10):1265-1276. doi: 10.1177/02698811211032439. Epub 2021 Jul 24.
Aside from regulating circadian rhythms, melatonin also affects cognitive processes, such as alertness, and modulates the brain circuitry underlying psychiatric diseases, such as depression, schizophrenia and bipolar disorder, via mechanisms that are not fully clear. In particular, while melatonin MT1 receptors are thought primarily to mediate the circadian effects of the hormone, the contribution of the MT2 receptor to melatonin actions remains enigmatic.
To characterise the contribution of MT2 receptors to melatonin's effects on cognition and anxiety/sociability.
Mice with a genetic deletion of the MT2 receptor, encoded by the gene, were compared with wild-type littermates for performance in a translational touchscreen version of the continuous performance task (CPT) to assess attentional processes and then monitored over 3 days in an ethological home-cage surveillance system.
knockout (KO) mice were able to perform at relatively normal levels in the CPT. However, they showed consistent evidence of more liberal/risky responding strategies relative to control mice, with increases in hit rates and false alarm rates, which were maintained even when the cognitive demands of the task were increased. Assessment in the home-cage monitoring system revealed that female KO mice have increased anxiety levels, whereas male KO mice show increased sociability.
The results confirm that the MT2 receptor plays a role in cognition and also modulates anxiety and social interactions. These data provide new insights into the functions of endogenous melatonin and will inform future drug development strategies focussed on the MT2 receptor.
除了调节昼夜节律外，褪黑素还通过其作用机制影响认知过程，如警觉性，并调节抑郁症、精神分裂症和双相情感障碍等精神疾病的大脑回路。特别是，虽然认为褪黑素 MT1 受体主要介导激素的昼夜节律作用，但 MT2 受体对褪黑素作用的贡献仍然是个谜。
描述 MT2 受体对褪黑素认知和焦虑/社交作用的贡献。
将编码基因缺失 MT2 受体的基因敲除（KO）小鼠与野生型同窝仔鼠进行比较，以评估其在连续表现任务（CPT）的转化触摸屏版本中的注意力过程表现，然后通过行为学的家庭笼监测系统监测 3 天。
KO 小鼠在 CPT 中能够相对正常地表现。然而，与对照小鼠相比，它们表现出一致的更宽松/冒险的反应策略的证据，表现为击中率和虚报率增加，即使任务的认知要求增加，这些增加仍得以维持。家庭笼监测系统的评估显示，雌性 KO 小鼠的焦虑水平升高，而雄性 KO 小鼠的社交能力增强。
这些结果证实了 MT2 受体在认知中发挥作用，并调节焦虑和社交互动。这些数据为内源性褪黑素的功能提供了新的见解，并将为未来专注于 MT2 受体的药物开发策略提供信息。
