T-588, a cognitive enhancer, stimulates in vivo phosphorylation of extracellular signal-regulated kinases in the hippocampus

Administration of (1R)-1-benzo[b]thiophen-5-yl-2-[2-(diethylamino)ethoxy]ethan-1-ol hydrochloride (T-588), a cognitive enhancer, like the acetylcholine esterase inhibitors physostigmine and tacrine, stimulated phosphorylation of extracellular signal-regulated kinases (ERK) in the mouse hippocampus. The effect of T-588 on ERK phosphorylation was persistent from 2 to 6 h after injection. Immunohistochemical study showed that T-588 stimulated neuronal ERK phosphorylation in rat hippocampal CA1 pyramidal subfield. These findings suggest that systemic T-588 stimulates the ERK kinase pathway in the hippocampal neurons. (C) 2003 Elsevier B.V. All rights reserved.