Effects of pretreatment with LY2090314, a potent glycogen synthase kinase-3 inhibitor, on methamphetamine-induced hyperlocomotion and stereotypy in mice

Abstract

Glycogen synthase kinase-3 (GSK-3) is one of the most essential serine/threonine kinases, which are constitutively active, multifaceted, and ubiquitous in nature. In mammalian cells, GSK-3 is formed as the two isoforms termed GSK-3a and GSK-3b. GSK-3b is present in a high concentration in the abundance of tissues in the central nervous system, regulating a crucial role in neuronal signaling pathways. The research for involvement of GSK-3b signaling in drug abuse liability has been progressed based on the studies investigating molecular and cellular mechanism of action, but few reports have been made on animal research so far. In this presentation, we will demonstrate that pretreatment with LY2090314 (2.5, 10, 25 mg/kg), a potent GSK-3b inhibitor, tended to have an inhibitory effect on methamphetamine (METH; 3 mg/kg)-induced hyperlocomotion. For stereotyped behavior (10 mg/kg of METH), LY2090314 significantly inhibited METH-induced stereotypy in a dose-dependent fashion. Stereotyped biting was significantly reduced by doses of LY2090314. These results suggest that GSK-3 signaling pathway is essential for the expression of METH-induced stereotypy.