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The effect of age on pilocarpine-induced expression of the immediate-early gene c-fos was examined in the hippocampus and cortex of Long-Evans rats. Rats were treated with either pilocarpine (25 mg/kg) or saline, and sacrificed 90 min. following injection. The level of c-fos mRNA and Fos-like protein expression was determined using in situ hybridization histochemistry, and immunocytochemistry, respectively. In saline-treated animals, comparable levels of c-fos mRNA and Fos-like protein were observed in the hippocampus and cortical regions of young (6 month) and aged (24-26 months) rats. The expression of Fos-like protein following pilocarpine treatment was increased, however, in frontal, retrosplenial, and cingulate cortex of aged compared to young rats. In frontal and retrosplenial cortex, the changes in Fos-like protein were accompanied by changes in c-fos mRNA expression. In contrast, no age difference was detected in the hippocampus or parietal cortex of pilocarpine-treated rats. These regionally-specific age differences in response to pilocarpine administration suggest that mechanisms localized to those areas play an important role in determining the response to cholinergic stimulation mediated through post-synaptic muscarinic receptors.