D1 receptor hypersensitivity in mice with low striatal D2 receptors facilitates select cocaine behaviors.

ABSTRACT: Vulnerability for cocaine abuse in humans is associated with low dopamine D2 receptor (D2R) availability in the striatum. The mechanisms driving this vulnerability are poorly understood. In this study, we found that downregulating D2R expression selectively in striatal indirect-pathway neurons triggers a multitude of changes in D1 receptor (D1R)-expressing direct-pathway neurons, which comprise the other main subpopulation of striatal projection neurons. These changes include a leftward shift in the dose-response to a D1-like agonist that indicates a behavioral D1R hypersensitivity, a shift from PKA to ERK intracellular signaling cascades upon D1R activation, and a reduction in the density of bridging collaterals from D1R-expressing neurons to pallidal areas. We hypothesize that the D1R hy

SUBMITTER: Dobbs LK 

PROVIDER: S-EPMC6372593 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature