Date of Award
Mice that are incapable of expressing the small G protein Rhes have been generated and have shown to have abnormalities in behaviors mediated by the striatum, a region in which Rhes is highly expressed. Moreover, conditions that result in dopamine supersensitivity and a breakdown in D1/D2 synergism in rodents, consistently decrease rhes mRNA in striatum. Thus, Rhes may play have relevance in dopamine signal modulation. For evaluating the role of Rhes in anxiety, stereotypy and basal motor activity, adult male and female wild-type (WT) mice, Rhes knockout (KO) mice, and mice heterozygous for the KO and WT alleles (Het) were tested. There was no genotype differences in the distance traveled in the open field. However, female KO mice showed lower anxiety than either WTs or Hets, based on the quantity of time spent in the periphery vs. the central area of the open field (p<0.05). With respect to striatally-mediated motor stereotypy, the mixed D1/D2 agonist apomorphine elicited a significant greater response in male KO and Het compared to WTs (p<0.05). In previous studies of D1/D2 synergism, it has been consistently found in rats and mice that when D2 receptors alone are stimulated, there is an early and brief, D1 independent peak in stereotypy that disappears by 20 minutes. In the present study, this effect was more intense in male KO mice compared to the other two genotypes during the interval between 5 and 10 minutes (p<0.05). The current findings favor the hypothesis that the GTP-binding protein Rhes interacts with as yet unidentified cellular proteins to buffer the transduction of synaptic dopamine signals into intracellular responses. Decreased or loss of Rhes therefore results in increased DA signal transduction.
Quintero, Gabriel, "Interactions of the Striatal Gene Rhes with the Dopaminergic System in Rodents" (2007). University of New Orleans Theses and Dissertations. 621.