Investigations of the cholinergic deficit hypothesis in the hippocampus of the aged rat brain with physostigmine and scopolamine.

Using histochemically demonstrated acetylcholinesterase activity and (14)C-2-deoxyglucose uptake as the respective indices, a study was set up to determine whether cerebral (hippocampal) metabolism was stimulated by a cholinergic agonist and/or inhibited by a cholinergic antagonist. For this 36 12-month-old (adult) and 48 27-month-old (aged) Fischer 344 rats were given intraperitoneal injections of physostigmine 0.05, 0.1 or 0.2 mg/kg or scopolamine 0.01, 0.03 or 0.1 mg/kg for 5 days. In the aged rats there was a slight increase in acetylcholinesterase activity after physostigmine but no convincing evidence of enhanced (14)C-2-deoxyglucose uptake. In neither age group was glucose uptake significantly reduced by scopolamine; it was in fact increased, as was - slightly but significantly - acetylcholinesterase activity. Findings for acetylcholinesterase activity and (14)C-2-deoxyglucose uptake in aged Fischer 344 rats thus do not provide firm corroboration of physostigmine-induced stimulation of mental performance found in behavioural studies, while scopolamine did not adversely affect the hippocampal variables studied. It is concluded that cholinergic agents such as physostigmine and scopolamine have only a marginal effect on the functional and metabolic deficits associated with cerebral aging.