The striatal-enriched protein Rhes is a critical modulator of cocaine-induced molecular and behavioral responses

摘要: Previous evidence pointed out a role for the striatal-enriched protein Rhes in modulating dopaminergic transmission. Based on knowledge that cocaine induces both addiction and motor stimulation, through its ability to enhance signaling corpus striatum, we have now explored involvement of effects associated with this psychostimulant. Our behavioral data showed lack knockout animals caused profound alterations stimulation following exposure, eliciting significant leftward shift dose-response curve triggering dramatic hyperactivity. We also found modulated either short- or long-term sensitization induced by cocaine, since prevents them mutants. Consistent vivo observation, mice greater increase striatal cocaine-dependent D1R/cAMP/PKA signaling, along considerable enhancement Arc, zif268, Homer1 mRNA expression. documented produced cocaine-related proteomic profiling, differential expression proteins clustering calcium homeostasis cytoskeletal binding categories. Despite our did not reveal any changes midbrain neurons as affect: (i) DAT activity; (ii) D2R-dependent regulation GIRK; (iii) dopamine release. Collectively, results strengthen view acts pivotal physiological “molecular brake” system overactivation psychostimulants, thus making interest regulating molecular mechanism underpinning stimulatory effects.