The roles of glial cell line-derived neurotrophic factor, tumor necrosis factor-α, and an inducer of these factors in drug dependence

Minae Niwa, Atsumi Nitta, Kiyofumi Yamada, Toshitaka Nabeshima

研究成果: Review article

32 引用 (Scopus)

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There are few efficacious medications for drug dependence at present. Recent evidence has suggested that various cytokines are involved in the effects of abused drugs, suggesting that these factors play a role in drug dependence. In this article, the roles of glial cell line-derived neurotrophic factor (GDNF) and tumor necrosis factor-α (TNF-α) in drug dependence are discussed. GDNF inhibits the cocaine-induced upregulation of tyrosine hydroxylase activity in the ventral tegmental area and blocks behavioral responses to cocaine. TNF-α attenuates rewarding effects and locomotor sensitization induced by methamphetamine (METH) and morphine (MOR). Moreover, we mentioned the potential of Leu-Ile, which induces the expression of GDNF and TNF-α, as a novel therapeutic agent for drug dependence. Leu-Ile inhibits not only the development but also the maintenance of METH- or MOR-induced place preference and locomotor sensitization in mice. The inhibitory effect of Leu-Ile on METH- or MOR-induced place preference is not observed in GDNF heterozygous and TNF-α knockout mice. Leu-Ile inhibits METH- or MOR-induced place preference and sensitization by attenuating the METH- or MOR-induced increase in extracellular dopamine levels in the nucleus accumbens via the induction of GDNF and TNF-α expression. These findings suggest that Leu-Ile could be a novel therapeutic agent for drug dependence.

元の言語English
ページ(範囲)116-121
ページ数6
ジャーナルJournal of Pharmacological Sciences
104
発行部数2
DOI
出版物ステータスPublished - 29-06-2007
外部発表Yes

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All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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