Clozapine shares a common signaling pathway (Akt/GSK pathway) with the mGluR2/3 agonist in normal rat PFC. Acute intraperitoneal administration of LY379268 (0.3 and 3.0 mg/kg) or clozapine (5 mg/kg) similarly affects the expression of GSK-3β and Akt. (a, b) The total protein levels of GSK-3β in all drug-treated groups were stable, without significant changes (P>0.05). In contrast, clozapine and both doses of LY379268 significantly increased the expression of GSK-3β Ser9 phosphorylation (P<0.05). Moreover, Akt was significantly increased in response to treatment with LY379268 (3.0 mg/kg) or clozapine (P<0.05) but was not altered by treatment with LY379268 at 0.3 mg/kg. The phosphorylation was, however, differentially and significantly changed by LY379268 at 0.3 mg/kg (increased almost twofold, P=0.010) and at 3.0 mg/kg (decreased, P=0.007) and decreased but not significantly by clozapine treatment (P=0.057). *P<0.05.