[Identification of Piccolo as a regulator of behavioral plasticity and dopamine transporter internalization].

Atsumi Nitta, Yoko Hibi, Yoshiaki Miyamoto, Toshitaka Nabeshima

研究成果: Review article

2 引用 (Scopus)

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Dopamine transporter (DAT) internalization is a mechanism underlying the decreased dopamine reuptake caused by addictive drugs like methamphetamine (METH). We found that Piccolo, a presynaptic scaffolding protein, was overexpressed in the nucleus accumbens (NAc) of the mice repeatedly administrated with METH. Piccolo downexpression by antisense technique augmented METH-induced behavioral sensitization, conditioned reward and synaptic dopamine accumulation in NAc. Expression of Piccolo C2A domain attenuated METH-induced inhibition of dopamine uptake in PC12 cells expressing human DAT. Consistent with this, it slowed down the accelerated DAT internalization induced by METH, thus maintaining the presentation of plasmalemmal DAT. In immunostaining and structural modeling Piccolo C2A domain displays an unusual feature of sequestering membrane phosphatidylinositol 4,5-bisphosphate, which may underlie its role in modulating DAT internalization. Together, our results indicate that Piccolo upregulation induced by METH represents a homeostatic response in the NAc to excessive dopaminergic transmission. Piccolo C2A domain may act as a cytoskeletal regulator for plasmalemmal DAT internalization, which may underlie its contributions in behavioral plasticity.

元の言語English
ページ(範囲)525-529
ページ数5
ジャーナルNihon Arukōru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence
45
発行部数6
出版物ステータスPublished - 01-12-2010
外部発表Yes

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All Science Journal Classification (ASJC) codes

  • Medicine(all)

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