Effects of T-588, a cognitive enhancer compound, on synaptic plasticity inthe dentate gyrus of freely moving rats

(1R)-1-benzo [b] thiophen-5-yl-2-[2-(diethylamino) ethoxy] ethan-1-ol hydro chloride (T-588) is a compound for the treatment of neurodegenerative disor ders, including Alzheimer's disease and cerebrovascular diseases. T-588 rep ortedly alleviates learning and memory deficits in animal models of dementi a. In the present study, we investigated the effects of T-588 on the induct ion and decay of long-term potentiation (LTP) and on the responses to paire d-pulse (pp) stimulation in freely moving rats. Perforant path-evoked field potentials were recorded in the dentate gyrus by chronically implanted ele ctrodes. LTP was induced by high-frequency stimulation 30 min after oral ad ministration of T-588 (0.3 or 3 mg/kg), T-588 significantly augmented the i ncrease in population spike amplitude and field excitatory postsynaptic pot ential slope after LTP induction, T-588 also prolonged the decay of augment ed population spike amplitude, but had no significant effect on the respons e to pp stimulation, These results suggest that T-588 facilitates long-term synaptic plasticity, but not shortterm synaptic plasticity in the dentate gyrus of freely moving rats. The effect of T-588 on long-term synaptic plas ticity may contribute to the alleviation of learning and memory dysfunction seen in animal models.