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

被引：122

作者：

Wand, G

Levine, M

Zweifel, L

Schwindinger, W

Abel, T

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA

[4] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA

[5] Weis Ctr Res, Geisinger Clin, Danville, PA 17822 USA

来源：

JOURNAL OF NEUROSCIENCE | 2001年 / 21卷 / 14期

关键词：

alcohol; sedation; adenylyl cyclase; protein kinase A; cAMP; alcoholism;

D O I：

10.1523/JNEUROSCI.21-14-05297.2001

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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 Gs alpha 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 Gs alpha 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.

引用

页码：5297 / 5303

页数：7

共 30 条

[1] Genetic demonstration of a role for PKA in the late phase of LTP and in hippocampus-based long-term memory [J].