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

Gary Wand, Michael Levine, Larry Zweifel, William Schwindinger, Ted Abel

Research output: Contribution to journalArticlepeer-review

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 Gsα 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 Gsα 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.

Original languageEnglish (US)
Pages (from-to)5297-5303
Number of pages7
JournalJournal of Neuroscience
Volume21
Issue number14
DOIs
StatePublished - Jul 15 2001

Keywords

  • Adenylyl cyclase
  • Alcohol
  • Alcoholism
  • Protein kinase A
  • Sedation
  • cAMP

ASJC Scopus subject areas

  • Neuroscience(all)

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