2. Academic Validation
  3. PPARγ/Adiponectin axis attenuates methamphetamine-induced conditional place preference via the hippocampal AdipoR1 signaling pathway

PPARγ/Adiponectin axis attenuates methamphetamine-induced conditional place preference via the hippocampal AdipoR1 signaling pathway

  • Prog Neuropsychopharmacol Biol Psychiatry. 2023 Mar 25;110758. doi: 10.1016/j.pnpbp.2023.110758.
Zongyue Sun 1,  Meiqin Wang 1,  Lei Xu 1,  Qiongyu Li 2,  Zhongyi Zhao 3,  Xuehao Liu 3,  Fantao Meng 4,  Jing Liu 4,  Wentao Wang 4,  Chen Li 5,  Shujun Jiang 6
Affiliations

Affiliations

  • 1 Department of Physiology, Binzhou Medical University, Shandong 264003, China; Medical Research Center, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China.
  • 2 Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Medical Research Center, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China.
  • 3 Department of Physiology, Binzhou Medical University, Shandong 264003, China.
  • 4 Medical Research Center, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China.
  • 5 Medical Research Center, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China. Electronic address: lc_0625@163.com.
  • 6 Department of Physiology, Binzhou Medical University, Shandong 264003, China. Electronic address: jiangshujun1@163.com.
PMID: 36972780 DOI: 10.1016/j.pnpbp.2023.110758
Abstract

Methamphetamine (METH) is a highly addictive psychostimulant. The adipocyte-derived hormone Adiponectin has a broad spectrum of functions in the brain. However, limited research has been conducted on the effect of Adiponectin signaling on METH-induced conditioned place preference (CPP) and knowledge of the underlying neural mechanisms is scarce. The METH induced adult male C57/BL6J mice model were used for testing the therapeutic activities of intraperitoneal injection of AdipoRon or Rosiglitazone, and AdipoR1 overexpression in hippocampal dentate gyrus (DG), and chemogenetic inhibiting the neural activity of DG, and the changes of Neurotrophic Factors, synaptic molecules, and glutamate receptors, and inflammatory cytokines were also measured. We found that Adiponectin expression was significantly reduced in METH addicted patients and mice. Our findings also showed that injection of AdipoRon or Rosiglitazone alleviated the METH-induced CPP behavior. Moreover, the expression of AdipoR1 in the hippocampus was also reduced, and AdipoR1 overexpression blocked the development of METH-induced CPP behavior through regulatory effects on Neurotrophic Factors, synaptic molecules, and glutamate receptors. The observed inhibitory neural activity of the hippocampal dentate gyrus (DG) induced via a chemogenetic approach produced a therapeutic effect on the METH-induced CPP behavior. Finally, we identified an abnormal expression of some key inflammatory cytokines through the PPARγ/Adiponectin/AdipoR1 axis. This study demonstrates that Adiponectin signaling is a promising diagnostic and therapeutic target for METH addiction.

Keywords

AdipoR1; Adiponectin; Conditioned place preference; Dentate gyrus; METH.

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