title: Intrastriatal gene delivery of GDNF persistently attenuates methamphetamine self-administration and relapse in mice.
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.
authors: Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Yijin
authors: Y
authors: Yan
authors: Yoshiaki
authors: Y
authors: Miyamoto
authors: Atsumi
authors: A
authors: Nitta
authors: Shin-Ichi
authors: S
authors: Muramatsu
authors: Keiya
authors: K
authors: Ozawa
authors: Kiyofumi
authors: K
authors: Yamada
authors: Toshitaka
authors: T
authors: Nabeshima
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000697:Central Nervous System Stimulants; D003342:Corpus Striatum / Q000378:metabolism*; D003463:Cues; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D058999:Drug-Seeking Behavior / Q000187:drug effects; D004777:Environment; D005108:Extinction, Psychological / Q000187:drug effects; D015316:Genetic Therapy / Q000379:methods*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D008845:Microinjections; D012054:Reinforcement, Psychology; D012646:Self Administration; D019966:Substance-Related Disorders / Q000401:mortality / Q000628:therapy*
chemical_list: D000697:Central Nervous System Stimulants; D051100:Glial Cell Line-Derived Neurotrophic Factor; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D008694:Methamphetamine