Cocaine effects on gene regulation in the striatum and behavior: increased sensitivity in D3 dopamine receptor-deficient mice.

Central effects of psychostimulants such as cocaine are predominantly mediated by dopamine receptors. We have used mice with a targeted deletion of the D3 dopamine receptor subtype to investigate the role of this receptor in the regulation of gene expression in striatal neurons and behavior by acute and repeated treatment with cocaine (25 mg/kg). In mice lacking D3 receptors, acute administration of cocaine has more pronounced stimulatory effects on c-fos and dynorphin expression in the dorsal and ventral striatum. The behavioral response to cocaine is also increased in these mice. These findings indicate that the D3 receptor plays an inhibitory role in the action of cocaine on behavior and gene regulation in the striatum.