RT Journal Article
SR Electronic
T1 Effects of T-588, a Cognitive Enhancer Compound, on Synaptic Plasticity in the Dentate Gyrus of Freely Moving Rats
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 354
OP 361
VO 298
IS 1
A1 Hidetoshi Yamaguchi
A1 Ryoi Tamura
A1 Jun-Ichi Kuriwaki
A1 Satoshi Eifuku
A1 Taketoshi Ono
YR 2001
UL http://jpet.aspetjournals.org/content/298/1/354.abstract
AB (1R)-1-benzo [b] thiophen-5-yl-2-[2-(diethylamino) ethoxy] ethan-1-ol hydrochloride (T-588) is a compound for the treatment of neurodegenerative disorders, including Alzheimer's disease and cerebrovascular diseases. T-588 reportedly alleviates learning and memory deficits in animal models of dementia. In the present study, we investigated the effects of T-588 on the induction and decay of long-term potentiation (LTP) and on the responses to paired-pulse (pp) stimulation in freely moving rats. Perforant path-evoked field potentials were recorded in the dentate gyrus by chronically implanted electrodes. LTP was induced by high-frequency stimulation 30 min after oral administration of T-588 (0.3 or 3 mg/kg). T-588 significantly augmented the increase in population spike amplitude and field excitatory postsynaptic potential slope after LTP induction. T-588 also prolonged the decay of augmented population spike amplitude, but had no significant effect on the response to pp stimulation. These results suggest that T-588 facilitates long-term synaptic plasticity, but not short-term synaptic plasticity in the dentate gyrus of freely moving rats. The effect of T-588 on long-term synaptic plasticity may contribute to the alleviation of learning and memory dysfunction seen in animal models. The American Society for Pharmacology and Experimental Therapeutics