1. Academic Validation
  2. Melatonin Regulates Neuronal Synaptic Plasticity in the Supramammillary Nucleus and Attenuates Methamphetamine-Induced Conditioned Place Preference and Sensitization in Mice

Melatonin Regulates Neuronal Synaptic Plasticity in the Supramammillary Nucleus and Attenuates Methamphetamine-Induced Conditioned Place Preference and Sensitization in Mice

  • J Pineal Res. 2024 Sep;76(6):e13006. doi: 10.1111/jpi.13006.
Qingyu Ren 1 Weikai Han 1 Yanan Yue 1 Yaqi Tang 1 Qingwei Yue 1 Stefano Comai 2 3 4 Jinhao Sun 1
Affiliations

Affiliations

  • 1 Department of Anatomy and Neurobiology, Shandong University School of Basic Medicine, Jinan, Shandong, China.
  • 2 Department of Psychiatry, McGill University, Montréal, Quebec, Canada.
  • 3 Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy.
  • 4 Department of Biomedical Sciences, University of Padua, Padua, Italy.
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 CA2+ levels in the SuM and reversed METH-induced addictive behavior, effects that were blocked with the selective MT2 receptors antagonist 4P-PDOT and the MT1 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.

Keywords

addiction; melatonin; methamphetamine; supramammillary nucleus; synaptic plasticity.

Figures
Products