Viral restoration of dopamine to the nucleus accumbens is sufficient to induce a locomotor response to amphetamine.
Administration of amphetamine to mice evokes hyperlocomotion. Dopamine deficient (DD) mice, in which tyrosine hydroxylase (TH) has been specifically inactivated in dopaminergic neurons, have a blunted response to amphetamine, indicating that the hyperlocomotive response requires dopamine. Dopamine production can be restored to specific brain regions by using adeno-associated viruses expressing TH and GTP cyclohydrolase 1 (GTPCH1). Restoration of dopamine specifically to the nucleus accumbens (NAc) of DD mice completely restores the ability of these mice to respond to amphetamine. This response is specific to the dopamine production in the NAc, as restoration of dopamine production to the caudate putamen (CPu) does not fully restore the hyperlocomotive response to amphetamine. These data support previous studies in which accumbal dopamine is required for producing a normal locomotor response to amphetamine and further show that release of dopamine restricted to the NAc is sufficient for this response
Heusner
Carrie L
CL
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Hnasko
Thomas S
TS
Szczypka
Mark S
MS
Liu
Yuhong
Y
During
Matthew J
MJ
Palmiter
Richard D
RD
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000229:Dependovirus / Q000235:genetics*; D004298:Dopamine / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D009043:Motor Activity / Q000235:genetics* / Q000502:physiology; D009714:Nucleus Accumbens / Q000378:metabolism / Q000502:physiology*; D011995:Recombination, Genetic
D000661:Amphetamine; D004298:Dopamine