The cAMP-protein kinase A signal transduction pathway modulates ethanol consumption and sedative effects of ethanol.
J Neurosci
; 21(14): 5297-303, 2001 Jul 15.
Article
in En
| MEDLINE
| ID: mdl-11438605
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Alcohol Drinking
/
Signal Transduction
/
Central Nervous System Depressants
/
Cyclic AMP-Dependent Protein Kinases
/
GTP-Binding Protein alpha Subunits, Gs
/
Heterotrimeric GTP-Binding Proteins
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Ethanol
/
Nerve Tissue Proteins
Limits:
Animals
Language:
En
Journal:
J Neurosci
Year:
2001
Document type:
Article
Affiliation country:
Estados Unidos
Country of publication:
Estados Unidos