Effect of oxiracetam and piracetam on central cholinergic mechanisms and active-avoidance acquisition.
Oxiracetam at 100 and 300 mg/kg i.p. dose levels increased acetylcholine (ACh) utilization in the rat cerebral cortex and hippocampus. ACh utilization was assessed by measuring, with a gas chromatographic method, the decrease in ACh level after inhibiting its synthesis by 15 micrograms intracerebroventricularly (i.c.v.) injection of hemicholinium (HC-3). ACh steady state levels were not affected. Piracetam (300 mg/kg i.p.) also increased ACh utilization in the hippocampus. Repeated daily administration of oxiracetam 100 mg/kg i.p. caused a 31% increase in high-affinity choline uptake (HACU) in the hippocampus. A single administration of 300 mg/kg i.p. of oxiracetam and piracetam also increased HACU rate in the hippocampus. However, the effect of piracetam was over within 3 h, while 3 h after its administration oxiracetam still caused a 40% increase in HACU rate. Oxiracetam (100 mg/kg i.p.) significantly antagonized the impairment in the acquisition of an active-avoidance conditioned response (pole climbing) associated with the inhibition of ACh synthesis by HC-3. These results indicate that oxiracetam enhances the activity of the septohippocampal cholinergic pathways, and to a lesser extent, of the cortical cholinergic network.
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D006426:Hemicholinium 3 / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D010889:Piracetam / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D011759:Pyrrolidines; D011760:Pyrrolidinones; D006426:Hemicholinium 3; D002794:Choline; D000109:Acetylcholine; C040619:oxiracetam; D010889:Piracetam