TY - JOUR T1 - The cAMP–Protein Kinase A Signal Transduction Pathway Modulates Ethanol Consumption and Sedative Effects of Ethanol JF - The Journal of Neuroscience JO - J. Neurosci. SP - 5297 LP - 5303 DO - 10.1523/JNEUROSCI.21-14-05297.2001 VL - 21 IS - 14 AU - Gary Wand AU - Michael Levine AU - Larry Zweifel AU - William Schwindinger AU - Ted Abel Y1 - 2001/07/15 UR - http://www.jneurosci.org/content/21/14/5297.abstract N2 - 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. ER -