Berry Raymond B, Chandra Dev, Diaz-Granados Jaime L, Homanics Gregg E, Matthews Douglas B
Department of Psychology, The University of Memphis, Memphis, TN 38152, USA.
Neurosci Lett. 2009 May 15;455(2):84-7. doi: 10.1016/j.neulet.2009.03.046. Epub 2009 Mar 17.
GABA(A) receptors, the major inhibitory receptors in the mammalian central nervous system, are affected by a number of drug compounds, including ethanol. The pharmacological effects of certain drugs have been shown to be dependent upon specific GABA(A) receptor subunits. Because benzodiazepines and ethanol have similar effect signatures, it has been hypothesized that these drugs share the gamma2-containing GABA(A) receptors as a mechanism of action. To probe the involvement of the gamma2 subunit in ethanol's actions, spatial memory for the Morris water maze task was tested in gamma2 heterozygous knockout mice and wild type littermate controls following ethanol administration at the following doses: 0.0, 1.25, 1.75, and 2.25 g/kg. While baseline learning and memory were unaffected by reduction of gamma2 containing GABA(A) receptors, ethanol dose-dependently impaired spatial memory equally in gamma2 heterozygous knockouts and wild type littermate controls.
GABA(A)受体是哺乳动物中枢神经系统中的主要抑制性受体,受到包括乙醇在内的多种药物化合物的影响。某些药物的药理作用已被证明取决于特定的GABA(A)受体亚基。由于苯二氮䓬类药物和乙醇具有相似的效应特征,因此有人推测这些药物共享含γ2的GABA(A)受体作为一种作用机制。为了探究γ2亚基在乙醇作用中的参与情况,在给予以下剂量的乙醇后,对γ2杂合敲除小鼠和野生型同窝对照小鼠进行了Morris水迷宫任务的空间记忆测试:0.0、1.25、1.75和2.25 g/kg。虽然基线学习和记忆不受含γ2的GABA(A)受体减少的影响,但乙醇剂量依赖性地损害γ2杂合敲除小鼠和野生型同窝对照小鼠的空间记忆,且损害程度相同。