2008年3月
Regulation of psychostimulant-induced signaling and gene expression in the striatum
JOURNAL OF NEUROCHEMISTRY
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- 巻
- 104
- 号
- 6
- 開始ページ
- 1440
- 終了ページ
- 1449
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1111/j.1471-4159.2008.05240.x
- 出版者・発行元
- BLACKWELL PUBLISHING
Amphetamine (AMPH) and cocaine are indirect dopamine agonists that activate multiple signaling cascades in the striatum. Each cascade has a different subcellular location and duration of action that depend on the strength of the drug stimulus. In addition to activating D1 dopamine-Gs-coupled-protein kinase A signaling, acute psychostimulant administration activates extracellular-regulated kinase transiently in striatal cells; conversely, inhibition of extracellular-regulated kinase phosphorylation decreases the ability of psychostimulants to elevate locomotor behavior and opioid peptide gene expression. Moreover, a drug challenge in rats with a drug history augments and prolongs striatal extracellular-regulated kinase phosphorylation, possibly contributing to behavioral sensitization. In contrast, AMPH activates phosphoinositide-3 kinase substrates, like protein kinase B/Akt, only in the nuclei of striatal cells but this transient increase induced by AMPH is followed by a delayed decrease in protein kinase B/Akt phosphorylation whether or not the rats have a drug history, suggesting that the phosphoinositide-3 kinase pathway is not essential for AMPH-induced behavioral sensitization. Chronic AMPH or cocaine also alters the regulation of inhibitory G protein-coupled receptors in the striatum, as evident by a prolonged decrease in the level of regulator of G protein signaling 4 after non-contingent or contingent (self-administered) drug exposure. This decrease is exacerbated in behaviorally sensitized rats and reversed by re-exposure to a cocaine-paired environment. A decrease in regulator of G protein signaling 4 levels may weaken its interactions with metabotropic glutamate receptor 5, G alpha q, and phospholipase C beta that may enhance drug-induced signaling. Alteration of these protein-protein interactions suggests that the striatum responds to psychostimulants with a complex molecular repertoire that both modulates psychomotor effects and leads to long-term neuroadaptations.
- リンク情報
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- DOI
- https://doi.org/10.1111/j.1471-4159.2008.05240.x
- CiNii Articles
- http://ci.nii.ac.jp/naid/80019374114
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/18221378
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000253628700003&DestApp=WOS_CPL
- ID情報
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- DOI : 10.1111/j.1471-4159.2008.05240.x
- ISSN : 0022-3042
- CiNii Articles ID : 80019374114
- PubMed ID : 18221378
- Web of Science ID : WOS:000253628700003