Dept of Behavioral Neuroscience and Portland Alcohol Research Center, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
Behav Brain Res. 2013 Jan 15;237:49-58. doi: 10.1016/j.bbr.2012.09.006. Epub 2012 Sep 13.
Neural processes influenced by γ-aminobutyric acid B (GABA(B)) receptors appear to contribute to acute ethanol sensitivity, including the difference between lines of mice bred for extreme sensitivity (FAST) or insensitivity (SLOW) to the locomotor stimulant effect of ethanol. One goal of the current study was to determine whether selection of the FAST and SLOW lines resulted in changes in GABA(B) receptor function, since the lines differ in sensitivity to the GABA(B) receptor agonist baclofen and baclofen attenuates the stimulant response to ethanol in FAST mice. A second goal was to determine whether the baclofen-induced reduction in ethanol stimulation in FAST mice is associated with an attenuation of the mesolimbic dopamine response to ethanol. In Experiment 1, the FAST and SLOW lines were found to not differ in GABA(B) receptor function (measured by baclofen-stimulated [(35)S]GTPγS binding) in whole brain or in several regional preparations, except in the striatum in one of the two replicate sets of selected lines. In Experiment 2, baclofen-induced attenuation of the locomotor stimulant response to ethanol in FAST mice was not accompanied by a reduction in dopamine levels in the nucleus accumbens, as measured by microdialysis. These data suggest that, overall, GABA(B) receptor function does not play an integral role in the genetic difference in ethanol sensitivity between the FAST and SLOW lines. Further, although GABA(B) receptors do modulate the locomotor stimulant response to ethanol in FAST mice, this effect does not appear to be due to a reduction in tonic dopamine signaling in the nucleus accumbens.
γ-氨基丁酸 B（GABA(B)）受体影响的神经过程似乎有助于急性乙醇敏感性，包括对乙醇运动兴奋剂作用敏感（FAST）或不敏感（SLOW）的小鼠系之间的差异。当前研究的一个目标是确定 FAST 和 SLOW 系的选择是否导致 GABA(B)受体功能发生变化，因为这些系在对 GABA(B)受体激动剂巴氯芬的敏感性和巴氯芬减弱 FAST 小鼠对乙醇的兴奋剂反应方面存在差异。第二个目标是确定 FAST 小鼠中巴氯芬诱导的乙醇刺激减少是否与中脑边缘多巴胺对乙醇反应的减弱有关。在实验 1 中，发现整个大脑或几个区域制剂中，除了在两个重复选择系之一的纹状体中，FAST 和 SLOW 系之间的 GABA(B)受体功能（通过巴氯芬刺激的[(35)S]GTPγS 结合测量）没有差异。在实验 2 中，FAST 小鼠中巴氯芬诱导的对乙醇的运动兴奋剂反应的减弱并没有伴随着伏隔核多巴胺水平的降低，如通过微透析测量的那样。这些数据表明，总体而言，GABA(B)受体功能在 FAST 和 SLOW 系之间的乙醇敏感性遗传差异中不起关键作用。此外，尽管 GABA(B)受体确实调节 FAST 小鼠对乙醇的运动兴奋剂反应，但这种效应似乎不是由于伏隔核中紧张性多巴胺信号的降低。
