AGE-RELATED-CHANGES IN THE DENSITY OF MUSCARINIC CHOLINERGIC M(1) ANDM(2) RECEPTOR SUBTYPES IN PYRAMIDAL NEURONS OF THE RAT HIPPOCAMPUS

Age-dependent changes in the expression of muscarinic M(1) and M(2) ch olinergic receptors were assessed in the CA(1) and CA(3) fields of hip pocampus using radioligand binding and autoradiographic techniques wit h [H-3]-pirenzepine and [H-3]-AF-DX 116 as ligands. Male Wistar rats o f 2 months (young), 12 months (adult) and 27 months (old) of age were examined. Radioligand binding analysis revealed a significant decrease of the density of muscarinic M(1) cholinergic receptors with increasi ng age and no change in muscarinic M(2) cholinergic receptors. Autorad iographic evaluation of the number of silver grains developed within t he cell body of pyramidal neurons of the CA(1) and CA(3) fields reveal ed a decrease of muscarinic M(1) cholinergic receptors in the 27-month -old rats in comparison with younger cohorts and no changes in muscari nic M(2) cholinergic receptors. These findings suggest that the reduct ion of muscarinic M(1) sites noticed between rats of 2- and 12-months of age using radioligand binding techniques is probably dependent on t he loss of hippocampal neurons rather than on the reduction of recepto r density per neuron. Our data also indicate that appropriate morpholo gical techniques associated with quantitative analysis may be useful i n assessing age-dependent changes in the expression of neurotransmitte r receptors by specific neuronal populations. The possible pharmaco-th erapeutic relevance of the decreased expression of muscarinic M(1) cho linergic receptors by pyramidal neurons of the hippocampus of old rats is discussed.