Pathophysiology of “cholinoceptor supersensitivity” in affective disorders
Abstract
Phenomenological and physiological variables demonstrate supersensitive changes to cholinergic challenge in affective disorder subjects. Theorists generally assume the primary defect is the postsynaptic muscarinic receptor. However, in addition to defectiveness or up-regulation of this receptor, the appearance of postsynaptic "cholinoceptor supersensitivity" can result from abnormal presynaptic mechanisms, membrane "pathology," derangement of intrasystolic mechanisms that amplify effects of receptor-agonist coupling, or aberrant cholinergic-monoaminergic interaction. This article discusses abnormalities of the postsynaptic receptor, regulation of postsynaptic receptor density, the presynaptic muscarinic receptor, and other mechanisms regulating the release of acetylcholine, membrane dynamics, and "cascade" mechanisms-specifically the phosphatidylinositol (PI) cycle, Ca2+ mobilization, and cyclic guanosine monophosphate (GMP) generation-as causes of cholinergic system "supersensitivity." It is suggested that an approach to the topic emphasizing site of abnormality will encourage greater clarity of thought in the study of the cholinergic component of the pathophysiology of affective illness.
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Cholinergic hyperactivity plays a role in the pathophysiology of depression and can exacerbate depression-like symptoms in patients and controls.
“First, cholinergic hyperactivity plays a role in the pathophysiology of depression (2–4) and can exacerbate depression-like symptoms in patients and controls (4–6).”
From Persistent β <sub>2</sub> *-Nicotinic Acetylcholinergic Receptor Dysfunction in Major Depressive Disorder (2012) · cites this paper as [3]
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Drevets, W. C., Price, J. L., & Furey, M. L. (2008) · Brain Structure and Function · doi:10.1007/s00429-008-0189-x · Cited by 2,209 · see citing works
“Somatic antidepressant therapies may compensate for this dysfunction by modulating the pathological limbic activity which putatively mediates depressive symptoms (Drevets et al. 2002a) and the expression of neurotrophic/ neuroprotective factors that preserve the function of the MPFC (Manji et al.…”
BackgroundToward constructing an endophenotype strategy for bipolar disorders
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Antidepressant Effects of the Muscarinic Cholinergic Receptor Antagonist Scopolamine: A Review
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- Authors
- Dilsaver, S. C.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Dilsaver, Steven C
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 1986-07
- Volume
- 21
- Issue
- 8-9
- Pages
- 813-829
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2155322333
- Cited by
- 87
- References
- 162
- Citations by year
- 2021: 2 · 2020: 3 · 2019: 1 · 2018: 3 · 2017: 1 · 2016: 4 · 2015: 1 · 2014: 2 · 2013: 3 · 2012: 3
- FWCI
- 2.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- National Institute of Mental Health (SRC1K11 MH00553-01)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- cholinergic supersensitivity, mood disorders, muscarinic receptors, acetylcholine release, phosphatidylinositol cycle, calcium mobilization, cyclic GMP, membrane dynamics
- MeSH terms
- Affective Disorders, Psychotic, Biogenic Amines, Brain, Cell Membrane, Cyclic GMP, Humans, Synaptic Transmission, Terminology as Topic, Phosphatidylinositols, Receptors, Cholinergic, Receptors, Muscarinic, Synapses
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