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, 2022 02.
Article
em En
| MEDLINE
| ID: mdl-34871711
ABSTRACT
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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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Comportamento Animal
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Fosfoproteínas Fosfatases
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Neurônios Serotoninérgicos
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Núcleo Dorsal da Rafe
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Estimulantes do Sistema Nervoso Central
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Metanfetamina
Aspecto:
Patient_preference
Limite:
Animals
Idioma:
En
Revista:
Brain Res Bull
Ano de publicação:
2022
Tipo de documento:
Article