EFFECTS OF NICOTINAMIDE ON CENTRAL CHOLINERGIC TRANSMISSION AND ON SPATIAL-LEARNING IN RATS

High-dose nicotinamide (1000 mg/kg) leads to a minor increase of plasm a choline but to a major increase of the choline concentrations in the intra- and extracellular spaces of the brain. In the hippocampus, the nicotinamide-induced increase in choline was associated with an incre ase in the release of acetylcholine under stimulated conditions. In yo ung rats, nicotinamide in doses between 10 and 1000 mg/kg did not infl uence spatial learning, as tested in the Morris water maze. In old rat s, low doses of nicotinamide were ineffective whereas the high dose of 1000 mg/kg even impaired spatial learning. The combined administratio n of choline and nicotinamide had a synergistic effect on brain cholin e levels but had similar effects as nicotinamide given alone in the be havioural experiments. Additional tests for spontaneous behaviour and locomotion revealed procholinergic and sedative effects of the compoun d. We conclude that the ineffectiveness of the putative cognition enha ncer nicotinamide in the learning task may be due to the observed seda tive effect. Therefore, the development of nonsedative nicotinamide de rivatives is recommended.