ALTERED CHOLINERGIC METABOLISM IN RAT CNS FOLLOWING ALUMINUM EXPOSURE- IMPLICATIONS ON LEARNING-PERFORMANCE

The effects of Al on the central cholinergic system have been studied, Al, at a dose of 10 mg/kg of body weight/day for 4 weeks, had a delet erious effect on the activities of biosynthetic (choline acetyltransfe rase)and hydrolytic (acetylcholinesterase) enzymes of the neurotransmi tter acetylcholine. The levels of acetylcholine were also significantl y lowered in different brain regions at the end of the dose regimen. T here was a significant decrease in high-affinity choline uptake follow ing Al exposure. Muscarinic acetylcholine receptor binding studies rev ealed a decreased number of binding sites (B-max), with the maximum ef fects being manifested in the hippocampus. Exogenous addition of 10 mu M desferrioxamine restored the muscarinic receptor binding completely , The impaired cholinergic functioning had severe effects on cognitive functions. Neurobehavioral deficits were manifested in terms of decre ased active (52%) and passive (73.30%) avoidance tests. The results su ggest that Al exerts its toxic effects by altering cholinergic transmi ssion, which is ultimately reflected in neurobehavioral deficits.