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PMID: 11438605 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The cAMP-protein kinase A signal transduction pathway modulates ethanol consumption and sedative effects of ethanol.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 21 ·No. 14 ·2001-07-15 ·Pages 5297-303

Wand G, Levine M, Zweifel L, Schwindinger W, Abel T

Abstract

Ethanol and other drugs of abuse modulate cAMP-PKA signaling within the mesolimbic reward pathway. To understand the role of the cAMP-PKA signal transduction in mediating the effects of ethanol, we have studied ethanol consumption and the sedative effects of ethanol in three lines of genetically modified mice. We report that mice with the targeted disruption of one Gsalpha allele as well as mice with reduced neuronal PKA activity have decreased alcohol consumption compared with their wild-type littermates. Genetic reduction of cAMP-PKA signaling also makes mice more sensitive to the sedative effects of ethanol, although plasma ethanol concentrations are unaffected. In contrast, mice with increased adenylyl cyclase activity resulting from the transgenic expression of a constitutively active form of Gsalpha in neurons within the forebrain are less sensitive to the sedative effects of ethanol. Thus, the cAMP-PKA signal transduction pathway is critical in modulating sensitivity to the sedative effects of ethanol as well as influencing alcohol consumption.

MeSH Terms
Adenylyl Cyclases/metabolism Alcohol Drinking/genetics,metabolism Alleles Animals Behavior, Animal/drug effects,physiology Brain/drug effects,metabolism Central Nervous System Depressants/administration & dosage Chimera Choice Behavior/drug effects,physiology Chromogranins Crosses, Genetic Cyclic AMP-Dependent Protein Kinases/genetics,metabolism Drug Resistance/genetics Ethanol/administration & dosage,blood Female GTP-Binding Protein alpha Subunits, Gs Genetic Predisposition to Disease Heterotrimeric GTP-Binding Proteins/genetics,metabolism Heterozygote Male Mice Mice, Inbred C57BL Nerve Tissue Proteins Self Administration Signal Transduction/drug effects,physiology Sleep/drug effects
Chemicals
Central Nervous System Depressants Chromogranins Nerve Tissue Proteins Ethanol Cyclic AMP-Dependent Protein Kinases Gnas protein, mouse GTP-Binding Protein alpha Subunits, Gs Heterotrimeric GTP-Binding Proteins Adenylyl Cyclases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Wand G
Departments of Medicine, Psychiatry, and Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. [email protected]
Levine M
Zweifel L
Schwindinger W
Abel T
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Email
[email protected]
Published
2001-07-15
Pages
5297-303
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6762861
Subset
IM
Grants
NIAAA NIH HHS · AA09000 · United States
NIA NIH HHS · AG18199 · United States
NIDDK NIH HHS · DK18213 · United States
NICHD NIH HHS · HD26979 · United States
NIMH NIH HHS · MH60244 · United States
External Links
PubMed source PMC Full Text View journal details
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