Intracerebroventricular administration of ouabain, a Na/K-ATPase inhibitor, activates tyrosine hydroxylase through extracellular signal-regulated kinase in rat striatum

摘要: Alteration in dopamine neurotransmission has been reported to be involved the mania of bipolar disorder. Tyrosine hydroxylase (TH) is rate-limiting enzyme that crucial for biosynthesis, and its activity tightly regulated by phosphorylation at multiple N-terminal serine residues. Previously, we have intracerebroventricular (ICV) injection ouabain, a selective Na/K-ATPase inhibitor, induces hyperactivity rats mimics manic symptoms related activation extracellular signal-regulated protein kinase1/2 (ERK1/2), which plays roles modulation TH phosphorylation. In this study, investigated effects ICV ouabain on rat striatum involvement ERK1/2 ouabain-induced activation. induced an acute dose-dependent increase locomotor striatum. Ser19 was significantly increased with 100, 500, 1000μM Ser31 Ser40 500 1000μM. We also found pretreatment U0126, specific MEK1/2 attenuated Ser19, Ser31, Ser40, as well rats. Moreover, (Ser19, Ser40) maintained until 8h after single administration accompanied (Thr202/Tyr204) p90RSK (Thr359/Ser363). These findings imply signal pathway could play important role rats, model.