Effects of S 18986-1, a novel cognitive enhancer, on memory performances in an object recognition task in rats

( S)-2,3-dihydro-[3,4]cyclopentano-1,2,4-benzothiadiazine-1,1-dioxide (S 18986-1) is a new compound that facilitates post-synaptic responses by modulating α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-mediated synaptic responses and thus promotes long-term potentiation and po...

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Bibliographic Details
Published in:	European journal of pharmacology Vol. 401; no. 2; pp. 205 - 212
Main Authors:	Lebrun, Cécile, Pillière, Elisabeth, Lestage, Pierre
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier B.V 04-08-2000 Elsevier
Subjects:	Administration, Oral AMPA receptor Analysis of Variance Animals Benzothiadiazines - pharmacology Biological and medical sciences Dose-Response Relationship, Drug Injections, Intraperitoneal Male Medical sciences Memory Memory - drug effects Neuropharmacology Nootropic Agents - pharmacology Object recognition Pharmacology. Drug treatments Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) Psychology. Psychoanalysis. Psychiatry Psychomotor Performance - drug effects Psychopharmacology Pyrrolidinones - pharmacology Rat Rats Rats, Wistar S 18986-1 Time Factors AMPA receptor Rat S 18986-1 Object recognition Memory Psychotropic Rodentia Central nervous system Oral administration Cognition Glutamate receptor Aniracetam Catecholamine Biological activity Learning Postsynaptic Vertebrata Mammalia Animal Nootropic agent Norepinephrine Stimulus discrimination Comparative study Brain (vertebrata)
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Summary:	( S)-2,3-dihydro-[3,4]cyclopentano-1,2,4-benzothiadiazine-1,1-dioxide (S 18986-1) is a new compound that facilitates post-synaptic responses by modulating α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-mediated synaptic responses and thus promotes long-term potentiation and potentiates ( S)-AMPA-induced release of noradrenaline in rat brain slices. In the present study, the effects of S 18986-1 were evaluated on cognitive functions by using a one-trial object-recognition test in the Wistar rat, a test which measures a form of episodic memory in rodents. Recognition was measured by the ability of treated rats to discriminate between a familiar and a new object after a 24-h retention delay. Oral administrations with S 18986-1 (0.3 to 100 mg/kg) 1 h before each session of the test improved object recognition at concentrations as low as 0.3 mg/kg. Under the same conditions, the nootropic drug aniracetam was active at a dose of 10 mg/kg by i.p. route. S 18986-1 was still effective on the object-recognition test when it was administered 4 h before each of the three sessions. Furthermore, subchronic oral pretreatment (7 days) with S 18986-1 (0.3 to 30 mg/kg) also increased the recognition of the familiar object indicating that the animals failed to develop tolerance to repeated administrations with S 18986-1. Finally, the recognition of the familiar object was improved when S 18986-1 was administered before the recognition trial whereas the rats failed to recognise the familiar object when S 18986-1 was administered before the sample presentation trial only. Taken together, the results indicated that S 18986-1 facilitated a form of episodic memory in the rat, by improving the recognition of a familiar information (retention). Furthermore, S 18986-1 was long-acting and demonstrated a good oral bioavailability. These data confer on S 18986-1, a potential role in improving episodic memory impaired in neurodegenerative diseases and during aging.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0014-2999 1879-0712
DOI:	10.1016/S0014-2999(00)00429-5