Intrastriatal gene delivery of GDNF persistently attenuates methamphetamine self-administration and relapse in mice

Yijin Yan, Yoshiaki Miyamoto, Atsumi Nitta, Shin Ichi Muramatsu, Keiya Ozawa, Kiyofumi Yamada, Toshitaka Nabeshima

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Relapse of drug abuse after abstinence is a major challenge to the treatment of addicts. In our well-established mouse models of methamphetamine (Meth) self-administration and reinstatement, bilateral microinjection of adeno-associated virus vectors expressing GDNF (AAV-Gdnf) into the striatum significantly reduced Meth self-administration, without affecting locomotor activity. Moreover, the intrastriatal AAV-Gdnf attenuated cue-induced reinstatement of Meth-seeking behaviour in a sustainable manner. In addition, this manipulation showed that Meth-primed reinstatement of Meth-seeking behaviour was reduced. These findings suggest that the AAV vector-mediated Gdnf gene transfer into the striatum is an effective and sustainable approach to attenuate Meth self-administration and Meth-associated cue-induced relapsing behaviour and that the AAV-mediated Gdnf gene transfer in the brain may be a valuable gene therapy against drug dependence and protracted relapse in clinical settings.

Original languageEnglish
Pages (from-to)1559-1567
Number of pages9
JournalInternational Journal of Neuropsychopharmacology
Volume16
Issue number7
DOIs
Publication statusPublished - 01-08-2013

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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