S 18986, a positive modulator of AMPA receptors with cognition-enhancing properties, increases ACh release in the hippocampus of young and aged rat

This paper is in honour of Professor Manfred Zimmermann's 70th Birthday.
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Abstract

The effect of S 18986, positive AMPA receptor modulator, on acetylcholine (ACh), gamma-aminobutyric acid (GABA) and glutamate (Glu) release from the hippocampus of freely moving young and aged rats was investigated by microdialysis coupled to HPLC. The cognition-enhancing properties were evaluated by a passive avoidance test. In 3 month-old rats, S 18986 (10 mg/kg i.p.) increased by 70% ACh release, which returned to basal level within 2 h, while 3 mg/kg had no effect. In 22 month-old rats, both 3 and 10 mg/kg i.p. induced a long lasting increase in ACh release, as large as that induced by 10 mg/kg in young rats. S 18986 did not modify GABA and glutamate release. No effect on general behavior was observed, but S 18986 at both doses prevented the disrupting effect of scopolamine (1 mg/kg i.p.) on passive avoidance acquisition.

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Acknowledgements

The work was supported by a grant from the Institut de Recherches Internationales Servier.

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This paper is in honor of Professor Manfred Zimmermann's 70th birthday.

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Present address: Arizona Research Laboratories, Division of Neural Systems, Memory and Aging, University of Arizona, Tucson, AZ 85724, USA.

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