Suppression of RGSz1 function optimizes the actions of opioid analgesics by mechanisms that involve the Wnt/β-catenin pathway.

ABSTRACT: Regulator of G protein signaling z1 (RGSz1), a member of the RGS family of proteins, is present in several networks expressing mu opioid receptors (MOPRs). By using genetic mouse models for global or brain region-targeted manipulations of RGSz1 expression, we demonstrated that the suppression of RGSz1 function increases the analgesic efficacy of MOPR agonists in male and female mice and delays the development of morphine tolerance while decreasing the sensitivity to rewarding and locomotor activating effects. Using biochemical assays and next-generation RNA sequencing, we identified a key role of RGSz1 in the periaqueductal gray (PAG) in morphine tolerance. Chronic morphine administration promotes RGSz1 activity in the PAG, which in turn modulates transcription mediated by the Wnt/β-cateni

SUBMITTER: Gaspari S 

PROVIDER: S-EPMC5834666 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature