Oxiracetam and aniracetam increase acetylcholine release from the rat hippocampus "in vivo"

The effect of two nootropic drugs, oxiracetam and aniracetam, on cholinergic neurotransmission in vivo was investigated in the rat by means of the transversal microdialysis technique. The basal release of acetylcholine (ACh) from the hippocampus and parietal cortex was 2.93 +/- 0.17 and 3.10 +/- 0.18 pmol/20 min (mean +/- s.e.m.), respectively, and remained stable for at least 3 h, while the initial efflux of choline was 51.9 +/- 2.6 and 42.8 +/- 6.4 pmol/20 min (mean +/- s.e.m.), respectively, and decreased by about 50% during the first 60 min of collection. Oxiracetam, tested at doses of 50, 100, and 300 mg/kg ip, elicted a 63% increase in ACh release from the hippocampus at the dose of 100 mg/kg only. This effect of oxiracetam was inhibited by perfusion with tetrodotoxin (TTX), 5 x 10(-7) M. In oxiracetam-treated rats the decrease in choline efflux was less pronounced than in controls (-23% of the initial value) at the dose of 100 mg/kg. Aniracetam (100 mg/kg, orally) elicited a sustained increase of ACh release from the hippocampus (+58%, 120 min after the administration), without affecting choline efflux. Doses of 50 and 300 mg/kg, orally, of aniracetam were ineffective. Oxiracetam and aniracetam (50 and 100 mg/kg) neither modified the output of ACh or choline from the parietal cortex nor induced gross behavioral changes. These results indicate that oxiracetam and aniracetam could act on cognitive processes by stimulating the hippocampal cholinergic pathways.