title: The roles of glial cell line-derived neurotrophic factor, tumor necrosis factor-alpha, and an inducer of these factors in drug dependence.
abstract: 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-alpha (TNF-alpha) 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-alpha 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-alpha, 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-alpha 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-alpha expression. These findings suggest that Leu-Ile could be a novel therapeutic agent for drug dependence.
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan.
authors.forename: Minae
authors.initials: M
authors.lastname: Niwa
authors.forename: Atsumi
authors.initials: A
authors.lastname: Nitta
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamada
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nabeshima
mesh_terms: D000818:Animals; D004151:Dipeptides / Q000494:pharmacology*; D051098:Glial Cell Line-Derived Neurotrophic Factors / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008694:Methamphetamine / Q000494:pharmacology; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D051381:Rats; D019966:Substance-Related Disorders / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000502:physiology
chemical_list: D004151:Dipeptides; D051098:Glial Cell Line-Derived Neurotrophic Factors; D009294:Narcotics; D014409:Tumor Necrosis Factor-alpha; C492946:leucyl-isoleucyl; D008694:Methamphetamine; D009020:Morphine