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.
Herzog
Christopher D
CD
Department of Psychology, The Ohio State University, 31 Townshend Hall, 1885 Neil Avenue, Columbus, OH 43210, USA. cherzog@ceregene.com
Nowak
Kelly A
KA
Sarter
Martin
M
Bruno
John P
JP
D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000378:metabolism; D000344:Afferent Pathways / Q000378:metabolism; D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D002799:Cholinergic Fibers / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D017551:Microdialysis / Q000379:methods; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D000110:Acetylcholinesterase; D000109:Acetylcholine; D011188:Potassium