Comparison of single vs. multiple administrations of the AMPA receptors modulator S 18986 in the object recognition task in rats

• Published in: Fundamental & clinical pharmacology Vol. 21; no. 4; pp. 349 - 354
• Main Authors: Bertaina-Anglade, V., Drieu la Rochelle, C., Muñoz, C., Morain, P., Bernard, K.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.2007; Blackwell
• Subjects: Allosteric Regulation; AMPA modulator; Animals; Benzothiadiazines - administration & dosage; Benzothiadiazines - pharmacology; Biological and medical sciences; cognitive enhancer; Dose-Response Relationship, Drug; Drug Administration Schedule; Exploratory Behavior - drug effects; Male; Medical sciences; Memory - drug effects; Nootropic Agents - administration & dosage; Nootropic Agents - pharmacology; object recognition task; Pharmacology. Drug treatments; Psychomotor Performance - drug effects; Rats; Rats, Sprague-Dawley; Receptors, AMPA - drug effects; S 18986; Time Factors; Modulator; Rat; Rodentia; Cognition; Glutamate receptor; S 18986; Multiple dose; Vertebrata; AMPA receptor; Mammalia; Animal; AMPA modulator; object recognition task; Comparative study; cognitive enhancer
• ISSN: 0767-3981; 1472-8206
• DOI: 10.1111/j.1472-8206.2007.00487.x

The present study aimed at defining the best scheme of administration of the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor‐positive modulator (S)‐2,3‐dihydro‐[3,4]‐cyclopentano‐1,2,4‐benzothiadiazine‐1,1‐dioxide (S 18986) [once daily (o.d.) administration of 1 mg/kg for 3 days vs. three times daily (t.i.d.) administration of 0.3 mg/kg for 3 days] to get an optimal procognitive activity in the object recognition task in rats. Memory performance [Recognition Index (RI)] of rats was significantly improved 1 h (RI = 41%, P < 0.01) and 3 h (RI = 46%, P < 0.001) following oral administration of S 18986 (1 mg/kg, o.d.) when compared with animals receiving the vehicle (RI = 6%). When the interval between administration and testing was increased to 6 h and 9 h, no statistically significant improvement in memory performance was observed (RI = 42% for 6 h and RI = 18% for 9 h vs. 20% for the vehicle group). When S 18986 was administered at 0.3 mg/kg t.i.d., no statistically significant improvement in memory performance was observed (RI = 36%). These findings show a long‐lasting efficacy of the AMPA receptor allosteric modulator in the object recognition task despite a short half‐life in plasma and in brain (approximately 1 h). Accordingly, multiple administrations of S 18986 are not required to obtain a maximal efficacy in this paradigm, because a o.d. schedule of administration leads to a powerful procognitive activity.