Effects of T-588, a cognitive enhancer compound, on synaptic plasticity in the dentate gyrus of freely moving rats.
(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.
Yamaguchi
H
H
Department of Physiology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
Tamura
R
R
Kuriwaki
J I
JI
Eifuku
S
S
Ono
T
T
D000818:Animals; D000697:Central Nervous System Stimulants / Q000737:chemistry / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects* / Q000502:physiology; D004048:Diethylamines / Q000737:chemistry / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D018697:Nootropic Agents / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology*
D000697:Central Nervous System Stimulants; D004048:Diethylamines; D018697:Nootropic Agents; D013876:Thiophenes; C082372:T 588