S 18986, a positive modulator of AMPA receptors with cognition-enhancing properties, increases ACh release in the hippocampus of young and aged rat.
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.
Rosi
Susanna
S
Department of Pharmacology, University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy.
Giovannini
Maria Grazia
MG
Lestage
Pierre J
PJ
Muñoz
Carmen
C
Corte
Laura Della
LD
Pepeu
Giancarlo
G
D000109:Acetylcholine / Q000378:metabolism*; D000375:Aging / Q000502:physiology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001581:Benzothiadiazines / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D017551:Microdialysis; D018697:Nootropic Agents / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D018091:Receptors, AMPA / Q000187:drug effects* / Q000378:metabolism; D012601:Scopolamine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D001581:Benzothiadiazines; D018690:Excitatory Amino Acid Agonists; D018697:Nootropic Agents; D018091:Receptors, AMPA; C414205:S18986-1; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D012601:Scopolamine; D000109:Acetylcholine