Background: In the previous meeting, we have demonstrated that pretreatment with Glycogen synthase kinase-3 inhibitors (GSK3i) suppress morphine-induced Straub's tail reaction (STR). In this presentation, we investigated the GSK3i mechanism of action. Methods: In this presentation, expression levels of GSK3beta and phosphorylated GSK3beta (pGSK3betaser9) were examined in the region of the striatum and nucleus accumbens and in the cerebral cortex after systemic morphine. In constipated mice after morphine, the effect of GSK3i on gastrointestinal transit was also examined to reveal whether the action of GSK3i on morphine effects was central and/or peripheral. Results: Pretreatment of mice with SB216763 (5 mg/kg, s.c.) or AR-A014418 (3 mg/kg, s.c.) significantly inhibited morphine-induced STR. In the brain regions tested, expression levels of pGSK3betaser9 in mice after morphine were not altered in mice treated with GSK3i in combination with morphine. The pretreatment with Gsk3i did not improve constipation in morphine-injected mice. Conclusions: The inhibitory effect of GSK3i on morphine-induced STR might not depend on the blockade of GSK3 in terms of phosphorylation levels of pGSK3betaser9. The mechanism of action is likely to be central but not peripheral.
