SDZ ENA 713 facilitates central cholinergic function and ameliorates spatial memory impairment in rats.
We have clarified the effects of SDZ ENA 713 (ENA), a new phenyl-carbamate derivative, on the spatial learning impairment and neurochemical indices of central cholinergic neurons in rats. Basal forebrain (BF) lesioning with ibotenic acid markedly impaired acquisition ability in the water maze task without changing swimming rates and decreased choline acetyltransferase (ChAT) activity in the frontal cortex of rats. ENA (0.1, 0.2 mg/kg, p.o.) significantly ameliorated the impairment in acquisition ability in a dose-dependent manner. At 0.2 mg/kg, ENA prevented the reduction in ChAT activity. In normal rats, ENA (1 mg/kg, p.o.) increased extracellular ACh concentration of the prefrontal cortex. On the other hand, tissue concentrations of norepinephrine, serotonin, dopamine and their metabolites were not changed in the frontal cortex, hippocampus and striatum of normal rats. These results suggest that ENA ameliorates spatial learning disability by not only facilitating the cholinergic transmission, but normalizing impaired ChAT activity in the learning-impaired rat model.
Ohara
T
T
Sandoz Tsukuba Research Institute, Department of Pharmacology, Japan.
Tanaka
K
K
Fukaya
H
H
Demura
N
N
Iimura
A
A
Seno
N
N
D000818:Animals; D001479:Basal Ganglia / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002219:Carbamates / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018680:Cholinergic Antagonists; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology; D017551:Microdialysis; D010275:Parasympathetic Nervous System / Q000187:drug effects* / Q000201:enzymology; D048448:Phenylcarbamates; D051381:Rats; D017208:Rats, Wistar; D000068836:Rivastigmine; D012601:Scopolamine; D013028:Space Perception / Q000187:drug effects*
D002219:Carbamates; D018680:Cholinergic Antagonists; D002800:Cholinesterase Inhibitors; D048448:Phenylcarbamates; D012601:Scopolamine; D002795:Choline O-Acetyltransferase; D000068836:Rivastigmine