Differences in muscarinic acetylcholine receptor subtypes in the central nervous system of long sleep and short sleep mice. [Ethanol effects]

Journal Article · Thu Feb 09 00:00:00 EST 1989 · FASEB Journal (Federation of American Societies for Experimental Biology); (USA)

OSTI ID:6831778

Watson, M; Ming, X; McArdle, J J ^[1]

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1. Univ of Medical, Newark, NJ (USA)

Differences in voluntary ethanol consumption have been noted in various inbred strains of mice and pharmacogenetic approaches have been used to study the mechanisms of action of many drugs such as ethanol. Long-sleep (LS) and short-sleep (SS) mice, selectively bred for differences in ethanol induced narcosis, provide a method by which a relationship between the differential responsiveness of these geno-types and muscarinic acetylcholine receptors (mAChR) may be evaluated. Sleep times after injection of 3ml ethanol/kg (i.p.) verified the higher sensitivity of LS vs. SS. Mean body weights of LS (26.5g) vs. SS (22g) were also significantly (p<.01) greater. Binding assays for ({sup 3}H)(-) quinuclidinylbenzilate (({sup 3}H)(-)QNB), a specific but nonsubtype selective mAChR antagonist, ({sup 3}H)pirenzepine (({sup 3}H)PZ), a specific M1 mAChR antagonist and ({sup 3}H)11-2-((2-((diethylamino) methyl)-1-piperidinyl) acetyl)-5,11-dihydro-6H-pyrido (2,3-b) (1,4) benzodiazepine-6-one, (({sup 3}H)AF-DX 116), an M2 selective antagonist were performed to determine mAChR affinity (K{sub d}) and density (B{sub max}) in CNS regions such as the cerebral cortex, hippocampus, corpus striatum and other areas. Significantly lower (30-40%) ({sup 3}H)(-)QNB binding suggests that SS have fewer mAChR's than LS in many areas. These differences may relate to their differential ethanol sensitivity.

• OSTI ID: 6831778
• Journal Information: FASEB Journal (Federation of American Societies for Experimental Biology); (USA), Vol. 3:3; ISSN 0892-6638
• Country of Publication: United States
• Language: English

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ETHANOL
TOXICITY
MICE
SENSITIVITY
ACETYLCHOLINE
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CENTRAL NERVOUS SYSTEM
COMPARATIVE EVALUATIONS
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AMMONIUM COMPOUNDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
DRUGS
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INTAKE
ISOTOPE APPLICATIONS
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
PARASYMPATHOMIMETICS
PROTEINS
QUATERNARY COMPOUNDS
RODENTS
VERTEBRATES
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