Aging-related differences in the ability of cortical cholinergic inputs to respond to local depolarization was assessed in young (3-6 months) and old (26-33 months) awake rats using in vivo microdialysis in the absence of an inhibitor of acetylcholinesterase. Rats were perfused, using a within-subjects, repeated session design, with vehicle (aCSF) or K(+) (25, 50, 100 mM). Perfusion of K(+) resulted in a dose-dependent increase in cortical ACh efflux with comparable efflux seen between the two ages following 25 mM (50%) and 50 mM (100%) K(+). In contrast, aged rats exhibited a marked attenuation (330%) in ACh efflux relative to young adult rats (650%). These data reveal aging-related decreases in the responsiveness of cortical cholinergic afferents, tested under physiologically relevant conditions, to local depolarization and may provide a neuronal mechanism contributing to the cognitive deficits reported in normal aging- and age-related pathological conditions.