MECAMYLAMINE OR SCOPOLAMINE-INDUCED LEARNING IMPAIRMENT - AMELIORATEDBY NEFIRACETAM

Nefiracetam is undergoing preclinical and clinical tests as a cognitio n-enhancing drug in Alzheimer's disease (AD). Nicotinic cholinergic re ceptors are lost in AD, and nicotinic as well as muscarinic cholinergi c receptors are involved in the modulation of eyeblink conditioning. E xperiments were carried out using young rabbits to examine the effect of nefiracetam on cholinergic antagonists to nicotinic (mecamylamine) and muscarinic (scopolamine) receptors. Rabbits were tested for 15 day s in the 750 ms delay eyeblink classical conditioning paradigm in pair ed and explicitly unpaired conditions. Nefiracetam at a dose of 15 mg/ kg significantly ameliorated the effects of 0.5 mg/kg mecamylamine, an d nefiracetam at a dose of 10 mg/kg significantly ameliorated the effe ct of 1.5 mg/kg scopolamine. The vehicle alone and nefiracetam alone g roups performed similarly to the groups treated with mecamylamine or s copolamine and nefiracetam. Reversal by nefiracetam of a nicotinic as well as a muscarinic cholinergic antagonist indicates that the drug ma y affect deficits specific to AD.