冰毒-
有条件地点偏好
甲基苯丙胺
神经科学
突触可塑性
敏化
敌手
NMDA受体
上瘾
谷氨酸受体
生物
药理学
化学
受体
生物化学
单体
有机化学
聚合物
丙烯酸酯
作者
Qingyu Ren,Weikai Han,Yuanzheng Yue,Yuchun Tang,Qingwei Yue,Stefano Comai,Jinhao Sun
摘要
ABSTRACT Methamphetamine (METH) is an addictive drug that threatens human health. The supramammillary nucleus (SuM) and its neural circuits play key roles in the regulation of spatial memory retrieval, and hippocampal contextual or social memory. Melatonin (MLT), a pineal hormone, can regulate hypothalamic‐neurohypophysial activity. Our previous study showed that MLT attenuates METH‐induced locomotor sensitization. However, whether MLT regulates SuM function and participates in METH‐induced contextual memory retrieval remains unclear. Using a mouse model of METH‐conditioned place preference (CPP) and sensitization, we found that METH activated c‐Fos expression and elevated calcium (Ca²⁺) levels in SuM neurons. Chemogenetic inhibition of SuM attenuates CPP and sensitization. Pretreatment with MLT decreased c‐Fos expression and Ca 2+ levels in the SuM and reversed METH‐induced addictive behavior, effects that were blocked with the selective MT 2 receptors antagonist 4P‐PDOT and the MT 1 receptors antagonist S26131. Furthermore, MLT reduced SuM synaptic plasticity, glutamate (Glu) release, and neuronal oscillations caused by METH, which were blocked by 4P‐PDOT. In conclusion, our data revealed that MLT regulates neuronal synaptic plasticity in the SuM, likely through the MLT receptors (MTs), and plays a role in modulating METH‐addictive behavior.
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