The Ras homolog Rhes affects dopamine D1 and D2 receptor-mediated behavior in mice

Dopamine activates five different receptor subtypes and a complex array of intracellular signaling pathways. Rhes is a striatally expressed guanidine triphosphate-binding protein involved in dopamine signaling. Here we have used mutant mice to test whether Rhes (Ras homolog enriched in striatum) is involved in D1 and D2 dopamine receptor-mediated behaviors. Rhes was not necessary for the expression of normal D1/D2 receptor synergism, as measured by apomorphine-induced stereotypy. The stereotypic responses to D1/D2 costimulation and to D2 stimulation alone were significantly increased in mice lacking Rhes, but D1 receptor-mediated grooming was reduced in these mice. These results suggest that Rhes is normally inhibitory to behaviors induced by D1/D2 receptor costimulation and by D2 receptor stimulation alone. Rhes, however, seems to facilitate the D1-specific behavior of grooming.