Microdialysis without acetylcholinesterase inhibition reveals an age-related attenuation in stimulated cortical acetylcholine release

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.