NK1 (TACR1) receptor gene 'knockout' mouse phenotype predicts genetic association with ADHD.

ABSTRACT: Mice with functional genetic ablation of the Tacr1 (substance P-preferring receptor) gene (NK1R-/-) are hyperactive. Here, we investigated whether this is mimicked by NK1R antagonism and whether dopaminergic transmission is disrupted in brain regions that govern motor performance. The locomotor activity of NK1R-/- and wild-type mice was compared after treatment with an NK1R antagonist and/or psychostimulant (d-amphetamine or methylphenidate). The inactivation of NK1R (by gene mutation or receptor antagonism) induced hyperactivity in mice, which was prevented by both psychostimulants. Using in vivo microdialysis, we then compared the regulation of extracellular dopamine in the prefrontal cortex (PFC) and striatum in the two genotypes. A lack of functional NK1R reduced (>50%) spontaneous dop

SUBMITTER: Yan TC 

PROVIDER: S-EPMC3943619 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature