Microdialysis without acetylcholinesterase inhibition reveals an age-related attenuation in stimulated cortical acetylcholine release
Abstract
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.
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The attribution of the cognitive effects of atropine and scopolamine to blockade of postsynaptic mAChRs must be modified by awareness that these drugs also increase the release of ACh due to presynaptic M2 receptor antagonism.
“However, the attribution of the cognitive effects to blockade of postsynaptic mAChRs must be modified by awareness that these drugs also increase the release of ACh, due to presynaptic M2 receptor antagonism (e.g., Herzog et al, 2003).”
From Modes and models of forebrain cholinergic neuromodulation of cognition (2011) · cites this paper as Herzog et al, 2003
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Modes and models of forebrain cholinergic neuromodulation of cognition
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- Authors
- Herzog, C.
- Affiliations
- The Ohio State University (US)
- Corresponding author
- Herzog, C
- ORCID
- Herzog, C
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2003-10
- Volume
- 24
- Issue
- 6
- Pages
- 861-863
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W1999299399
- Cited by
- 43
- References
- 15
- Citations by year
- 2023: 2 · 2020: 1 · 2019: 1 · 2016: 1 · 2014: 2 · 2013: 1 · 2012: 3
- FWCI
- 1.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ag010173-10)
- National Institute on Aging (AG10 173)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- acetylcholine release, aging, acetylcholinesterase inhibition, microdialysis, age-related cognitive decline, cholinergic neurotransmission, rats
- MeSH terms
- Acetylcholine, Acetylcholinesterase, Afferent Pathways, Age Factors, Aging, Analysis of Variance, Animals, Cholinergic Fibers, Dose-Response Relationship, Drug, Neurons, Potassium, Rats, Inbred F344, Prefrontal Cortex, Microdialysis, Rats
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