Enduring vulnerability to reinstatement of methamphetamine-seeking behavior in glial cell line-derived neurotrophic factor mutant mice

Yijin Yan, Kiyofumi Yamada, Minae Niwa, Taku Nagai, Atsumi Nitta, Toshitaka Nabeshima

研究成果: Article査読

48 被引用数 (Scopus)

抄録

Genetic factors are considered to play an important role in drug dependence/addiction including the development of drug dependence and relapse. With the use of a model of drug self-administration in mutant mice, several specific genes and proteins have been identified as potentially important in the development of drug dependence. In contrast, little is known about the role of specific genes in enduring vulnerability to relapse, a clinical hallmark of drug addiction. Using a mouse model of reinstatement, which models relapse of drug-seeking behavior in addicts, we provide evidence that a partial reduction in the expression of the glial cell line-derived neurotrophic factor (GDNF) potentiates methamphetamine (METH) self-administration, enhances motivation to take METH, increases vulnerability to drug-primed reinstatement, and prolongs cue-induced reinstatement of extinguished METH-seeking behavior. In contrast, there was no significant difference in novelty responses, METH-stimulated hyperlocomotion and locomotor sensitization, food-reinforced operant behavior and motivation, or reinstatement of food-seeking behavior between GDNF heterozygous knockout mice and wild-type littermates. These findings suggest that GDNF may be associated with enduring vulnerability to reinstatement of METH-seeking behavior and a potential target in the development of therapies to control relapse.

本文言語English
ページ(範囲)1994-2004
ページ数11
ジャーナルFASEB Journal
21
9
DOI
出版ステータスPublished - 07-2007
外部発表はい

All Science Journal Classification (ASJC) codes

  • バイオテクノロジー
  • 生化学
  • 分子生物学
  • 遺伝学

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