McCool Brian A, Frye Gerald D, Pulido Marisa D, Botting Shaleen K
Department of Medical Pharmacology and Toxicology, Texas A&M System H.S.C., College Station, TX 77843, USA.
Brain Res. 2003 Feb 14;963(1-2):165-77. doi: 10.1016/s0006-8993(02)03966-5.
It is well known that the anxiolytic potential of ethanol is maintained during chronic exposure. We have confirmed this using a light-dark box paradigm following chronic ethanol ingestion via a liquid diet. However, cessation from chronic ethanol exposure is known to cause severe withdrawal anxiety. These opposing effects on anxiety likely result from neuro-adaptations of neurotransmitter systems within the brain regions regulating anxiety. Recent work highlights the importance of amygdala ligand-gated chloride channels in the expression of anxiety. We have therefore examined the effects of chronic ethanol exposure on GABA(A) and strychnine-sensitive glycine receptors expressed by acutely isolated adult rat lateral/basolateral amygdala neurons. Chronic ethanol exposure increased the functional expression of GABA(A) receptors in acutely isolated basolateral amygdala neurons without altering strychnine-sensitive glycine receptors. Neither the acute ethanol nor benzodiazepine sensitivity of either receptor system was affected. We explored the likelihood that subunit composition might influence each receptor's response to chronic ethanol. Importantly, when expressed in a mammalian heterologous system, GABA(A) receptors composed of unique alpha subunits were differentially sensitive to acute ethanol. Likewise, the presence of the beta subunit appeared to influence the acute ethanol sensitivity of glycine receptors containing the alpha(2) subunit. Our results suggest that the facilitation of GABA(A) receptors during chronic ethanol exposure may help explain the maintenance of ethanol's anti-anxiety effects during chronic ethanol exposure. Furthermore, the subunit composition of GABA(A) and strychnine-sensitive glycine receptors may ultimately influence the response of each system to chronic ethanol exposure.
众所周知，乙醇的抗焦虑潜能在长期接触过程中得以维持。我们通过液体饮食长期摄入乙醇后，利用明暗箱范式证实了这一点。然而，已知长期乙醇接触停止会导致严重的戒断焦虑。对焦虑的这些相反作用可能源于调节焦虑的脑区内神经递质系统的神经适应性变化。最近的研究突出了杏仁核配体门控氯离子通道在焦虑表达中的重要性。因此，我们研究了长期乙醇接触对急性分离的成年大鼠外侧/基底外侧杏仁核神经元所表达的GABA(A)和士的宁敏感的甘氨酸受体的影响。长期乙醇接触增加了急性分离的基底外侧杏仁核神经元中GABA(A)受体的功能表达，而未改变士的宁敏感的甘氨酸受体。两种受体系统的急性乙醇敏感性和苯二氮䓬敏感性均未受影响。我们探究了亚基组成可能影响每个受体对长期乙醇反应的可能性。重要的是，当在哺乳动物异源系统中表达时，由独特α亚基组成的GABA(A)受体对急性乙醇的敏感性存在差异。同样，β亚基的存在似乎影响含有α(2)亚基的甘氨酸受体的急性乙醇敏感性。我们的结果表明，长期乙醇接触期间GABA(A)受体的促进作用可能有助于解释长期乙醇接触期间乙醇抗焦虑作用的维持。此外，GABA(A)和士的宁敏感的甘氨酸受体的亚基组成可能最终影响每个系统对长期乙醇接触的反应。
