Hyperactivity of the dopaminergic system in NTS1 and NTS2 null mice

Yanqi Liang, Mona Boules, Zhimin Li, Katrina Williams, Tomofumi Miura, Alfredo Oliveros, Elliott Richelson

研究成果: ジャーナルへの寄稿学術誌査読

35 被引用数 (Scopus)


Neurotensin (NT) is a tridecapeptide that acts as a neuromodulator in the central nervous system mainly through two NT receptors, NTS1 and NTS2. The functional-anatomical interactions between NT, the mesotelencephalic dopamine system, and structures targeted by dopaminergic projections have been studied. The present study was conducted to determine the effects of NT receptor subtypes on dopaminergic function with the use of mice lacking either NTS1 (NTS1-/-) or NTS2 (NTS2-/-). Basal and amphetamine-stimulated locomotor activity was determined. In vivo microdialysis in freely moving mice, coupled with HPLC-ECD, was used to detect basal and d-amphetamine-stimulated striatal extracellular dopamine levels. In vitro radioligand binding and synaptosomal uptake assays for the dopamine transporters were conducted to test for the expression and function of the striatal pre-synaptic dopamine transporter. NTS1-/- and NTS2-/- mice had higher baseline locomotor activity and higher basal extracellular dopamine levels in striatum. NTS1-/- mice showed higher locomotor activity and exaggerated dopamine release in response to d-amphetamine. Both NTS1-/- and NTS2-/- mice exhibited lower dopamine D1 receptor mRNA expression in the striatum relative to wild type mice. Dopamine transporter binding and dopamine reuptake in striatum were not altered. Therefore, lack of either NTS1 or NTS2 alters the dopaminergic system. The possibility that the dysregulation of dopamine transmission might stem from a deficiency in glutamate neurotransmission is discussed. The data strengthen the hypothesis that NT receptors are involved in the pathogenesis of schizophrenia and provide a potential model for the biochemical changes of the disease.

出版ステータス出版済み - 6月 2010

!!!All Science Journal Classification (ASJC) codes

  • 薬理学
  • 細胞および分子神経科学


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