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Publication : Effect of PPM1F in dorsal raphe 5-HT neurons in regulating methamphetamine-induced conditioned place preference performance in mice.

First Author  Liu Y Year  2022
Journal  Brain Res Bull Volume  179
Pages  36-48 PubMed ID  34871711
Mgi Jnum  J:352916 Mgi Id  MGI:7443295
Doi  10.1016/j.brainresbull.2021.12.001 Citation  Liu Y, et al. (2022) Effect of PPM1F in dorsal raphe 5-HT neurons in regulating methamphetamine-induced conditioned place preference performance in mice. Brain Res Bull 179:36-48
abstractText  Methamphetamine (METH), a synthetically produced central nervous system stimulant, is one of the most illicit and addictive drugs worldwide. Protein phosphatase Mg2 + /Mn2 + -dependent 1F F (PPM1F) has been reported to exert multiple biological and cellular functions. Nevertheless, the effects of PPM1F and its neuronal substrates on METH addiction remain unclear. Herein, we first established a METH-induced conditioned place preference (CPP) mouse model. We showed that PPM1F is widely distributed in 5-HT neurons of the dorsal raphe nucleus (DRN), and METH treatment decreased the expression of PPM1F in DRN, which was negatively correlated with METH-induced CPP behaviors. Knockout of PPM1F mediated by adeno-associated virus (AAV) in DRN produced enhanced susceptibility to METH-induced CPP, whereas the overexpression of PPM1F in DRN attenuated METH-induced CPP phenotypes. The expression levels of Tryptophan hydroxylase2 (TPH2) and serotonin transporter (SERT) were down-regulated with a concurrent reduction in 5-hydroxytryptamine (5-HT), tryptophan hydroxylase2 (TPH2)-immunoreactivity neurons and 5-HT levels in DRN of PPM1F knockout mice. In the end, decreased expression levels of PPM1F were found in the blood of METH abusers and METH-taking mice. These results suggest that PPM1F in DRN 5-HT neurons regulates METH-induced CPP behaviors by modulating the key components of the 5-HT neurotransmitter system, which might be an important pathological gene and diagnostic marker for METH-induced addiction.
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