Interactions between oxiracetam, aniracetam and scopolamine on behavior and brain acetylcholine.
The effect of cognition-enhancing agents oxiracetam and aniracetam on scopolamine-induced amnesia and brain acetylcholine decrease was investigated in the rat. Acetylcholine levels were measured by means of a gas-chromatographic method. Scopolamine (0.63 mg/kg IP 60 min before training) prevented the acquisition of a passive avoidance conditioned response ("step through": retest 30 min after training) and brought about a 64, 56 and 42% decrease in acetylcholine level in the cortex, hippocampus and striatum respectively. Oxiracetam (50 and 100 mg/kg IP) administered 30 min before scopolamine reduced the scopolamine-induced amnesic effect and decrease in acetylcholine level in the cortex and hippocampus, but not in the striatum. Lower and higher doses of oxiracetam were ineffective. Aniracetam (100 mg/kg PO) also prevented scopolamine-induced amnesia but attenuated acetylcholine decrease in the hippocampus only. Aniracetam (300 mg PO) reduced acetylcholine decrease in the hippocampus but did not prevent scopolamine-amnesia. In conclusion, oxiracetam and aniracetam exert a stimulatory effect on specific central cholinergic pathways. However, a direct relationship between cognition-enhancing properties and cholinergic activation needs further confirmation.
Spignoli
G
G
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
Pepeu
G
G
D000109:Acetylcholine / Q000032:analysis*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D012601:Scopolamine / Q000494:pharmacology*
D011759:Pyrrolidines; D011760:Pyrrolidinones; C036466:aniracetam; D012601:Scopolamine; D000109:Acetylcholine; C040619:oxiracetam