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mTOR signaling in the nucleus accumbens mediates behavioral sensitization to methamphetamine.
Huang, Shin-Han; Wu, Wan-Rong; Lee, Li-Ming; Huang, Pei-Rong; Chen, Jin-Chung.
Afiliación
  • Huang SH; Department of Physiology and Pharmacology, Graduate Institute of Biomedical Sciences, School of Medicine, Chang-Gung University, Taiwan.
  • Wu WR; Department of Physiology and Pharmacology, Graduate Institute of Biomedical Sciences, School of Medicine, Chang-Gung University, Taiwan.
  • Lee LM; Department of Biomedical Sciences, School of Medicine, Chang-Gung University, Taiwan.
  • Huang PR; Center for Molecular and Clinical Immunology, Chang-Gung University, Taiwan.
  • Chen JC; Department of Physiology and Pharmacology, Graduate Institute of Biomedical Sciences, School of Medicine, Chang-Gung University, Taiwan; Healthy Aging Research Center, Chang-Gung University, Taiwan; Neuroscience Research Center, Chang-Gung Memorial Hospital, Linkou, Taiwan; Chang-Gung Memorial Hospi
Prog Neuropsychopharmacol Biol Psychiatry ; 86: 331-339, 2018 08 30.
Article en En | MEDLINE | ID: mdl-29574227
Chronic psychostimulant treatment in rodents readily produces behavioral sensitization, which reflects altered brain function in response to repeated drug exposure. Numerous morphological and biochemical investigations implicate altered neural plasticity in striatal medium spiny neurons (MSNs) as an essential component in behavioral sensitization. The mammalian target of the rapamycin (mTOR) signaling pathway, a key regulator of synaptic neuroplasticity, in the ventral striatum of methamphetamine (METH) -sensitized mice was investigated to determine if a link exists with the development of METH sensitization. Behaviorally, METH-sensitized mice possessed increased levels of phosphorylated mTOR/S2448 and its down-stream regulator p70S6K and pS6 in the ventral striatum. Systemic treatment with rapamycin, a specific mTOR inhibitor, coincident with a daily METH injection suppressed the induction of METH sensitization and reduced the number of dendritic spines in the shell and core of the nucleus accumbens. The infusion of lentivirus-expressing mTOR-shRNA into the shell region of the nucleus accumbens inhibited the induction of behavioral sensitization to METH, which was comparable to the effect of rapamycin. These results suggest that mTORC1-mediated signaling in the nucleus accumbens mediates the development of behavioral sensitization to METH.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Serina-Treonina Quinasas TOR / Estimulantes del Sistema Nervioso Central / Metanfetamina / Actividad Motora / Núcleo Accumbens Límite: Animals / Humans / Male Idioma: En Revista: Prog Neuropsychopharmacol Biol Psychiatry Año: 2018 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Serina-Treonina Quinasas TOR / Estimulantes del Sistema Nervioso Central / Metanfetamina / Actividad Motora / Núcleo Accumbens Límite: Animals / Humans / Male Idioma: En Revista: Prog Neuropsychopharmacol Biol Psychiatry Año: 2018 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Reino Unido