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

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.