Effects of ?2-adrenoceptor agonists on locus coeruleus firing rate and brain noradrenaline turnover in N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)-treated rats
Abstract
Previous studies have shown that a low dose of the alkylating compound N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) reduces the density of alpha 2-adrenoceptors in rat cerebral cortex and antagonizes the effects of an alpha 2-adrenoceptor agonist on noradrenaline release in rat cortical slices. In the present study, a corresponding dose of EEDQ (1 mg/kg, s.c., 24 h) was shown to reduce the effect of the alpha 2-adrenoceptor agonists clonidine and guanfacine on noradrenaline turnover in rat brain while not affecting the inhibitory effect of clonidine on locus coeruleus (LC) cell firing. When considerably higher doses of EEDQ were administered (10 and 20 mg/kg, s.c., 24 h) not only the biochemical but also the electrophysiological effects of clonidine were markedly reduced (or even reversed). The data support the notion the EEDQ decreases the responsiveness of brain alpha 2-adrenergic receptors; moreover, they indicate that alpha 2-adrenoceptors regulating LC activity are characterized by a larger receptor reserve or are less sensitive to the influence of alkylation than are the population of alpha 2-adrenoceptors regulating noradrenaline utilization.
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Guanfacine has weaker actions at presynaptic α2-receptors, where its activity is only one-tenth that of clonidine.
“In addition, guanfacine has weaker actions at presynaptic α2-receptors, where its activity is only one-tenth that of clonidine (Engberg and Eriksson, 1991).”
From Catecholamine influences on prefrontal cortical function: Relevance to treatment of attention deficit/hyperactivity disorder and related disorders (2011) · cites this paper as Engberg and Eriksson, 1991
Stimulation of α2A-ARs reduces tonic firing of locus coeruleus neurons and thereby reduces norepinephrine release.
“Stimulation of α2A-ARs weakens amygdala function99, reduces stress-induced dopamine release in the PFC100 and reduces the tonic firing of locus coeruleus neurons and thus reduces norepinephrine release87,101.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [101]
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Noradrenergic modulation of functional brain networks underlying executive control
Breeden, A. L. (2016) · DigitalGeorgetown (Georgetown University Library)
- Authors
- Engberg, G., & Eriksson, E.
- Affiliations
- University of Gothenburg (SE)
- ORCID
- Eriksson, Elias
- Venue
- Naunyn-Schmiedeberg's Archives of Pharmacology
- Published
- 1991-05
- Volume
- 343
- Issue
- 5
- Pages
- 472-7
- ISSN
- 0028-1298 (ISSN-L)
- 1432-1912
- OpenAlex
- W2042468643
- Cited by
- 68
- References
- 29
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 4 · 2019: 1 · 2018: 3 · 2017: 1 · 2016: 2 · 2015: 5 · 2014: 7 · 2013: 1 · 2012: 4
- FWCI
- 0.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Naunyn-Schmiedeberg s Archives of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- alpha-2 adrenergic agonists, locus coeruleus, noradrenaline turnover, EEDQ, clonidine, guanfacine, alpha2-adrenoceptor antagonism, receptor alkylation, receptor reserve, noradrenaline release
- MeSH terms
- Animals, Brain, Clonidine, Dose-Response Relationship, Drug, Electrodes, Locus Coeruleus, Male, Norepinephrine, Quinolines, Rats, Inbred Strains, Receptors, Adrenergic, alpha, Guanfacine, Rats, In Vitro Techniques
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