Specific knockdown of the D2 long dopamine receptor variant.

Dopamine signaling in the nucleus accumbens is critical in mediating the effects of cocaine. There are two splice variants of dopamine D2 receptors, D2L and D2S, which are believed to have different functional roles. Here, we show, that knocking down D2L selectively using viral-mediated short-hairpin RNA led to a slight but significant decrease in basal locomotor activity with no significant change in cocaine-induced stimulation of locomotion. The knockdown appears to produce a trend of reduced conditioned place preference to cocaine but the difference was not statistically significant. Our results demonstrated that the splice variants of D2 receptors can be selectively manipulated in vivo in specific brain regions allowing more specific studies of each D2 receptor isoform.