Changes in regional cerebral metabolic rates for glucose produced by the serotonin agonist m-chlorophenylpiperazine (m-CPP) are reduced by chronic pretreatment with m-CPP in both young and old rats, demonstrating preservation of serotonin regulation during aging. The metabolic effects of m-CPP depend upon adrenal function. In a model of cholinergic cortical deafferentation, produced by lesioning the nucleus basalis magnocellularis cerebral metabolic deficits were smaller in aged rats, demonstrating an age-related reduction in tonic cholinergic input to the neocortex. Metabolic responses to cholinergic drugs were preserved in this model, indicating presynaptic reorganization also manifest as altered regional brain functional interactions.