Indiana Alcohol Research Center and Department of Psychology, Indiana University - Purdue University Indianapolis, Indianapolis, IN 46202, USA.
Indiana Alcohol Research Center and Department of Psychology, Indiana University - Purdue University Indianapolis, Indianapolis, IN 46202, USA.
Behav Brain Res. 2022 Feb 10;418:113631. doi: 10.1016/j.bbr.2021.113631. Epub 2021 Oct 26.
The dorsolateral striatum (DLS) is involved in addiction, reward, and alcohol related behaviors. The DLS primarily receives excitatory inputs which are gated by post-synaptic AMPA receptors. We antagonized AMPA receptors in the DLS to investigate how such modulation affects binge-like alcohol drinking in male and female C57BL/6J mice and whether an associated alcohol drinking history alters dorsomedial striatum (DMS) and DLS AMPA receptor expression. We also investigated the effect of intra-DLS NBQX on locomotor activity and saccharin drinking in mice. Mice were allowed free access to 20% alcohol for two hours each day for a total of seven days. Mice received an intra-DLS infusion of one of four concentrations of NBQX (saline, 0.15, 0.5, or 1.5 μg/side), an AMPA receptor antagonist, immediately prior to alcohol access on day 7. Two-hour binge alcohol intakes, locomotor activity, and blood alcohol concentrations were determined. Intra-DLS NBQX reduced binge-like alcohol drinking in a U-shaped manner in male and female mice. Intake predicted blood alcohol concentration, and locomotor activity was not affected. In a follow up experiment, we assessed whether the most effective NBQX concentration for reducing alcohol consumption also reduced saccharin drinking, finding intra-DLS NBQX did not alter saccharin drinking in male and female mice. These data suggest that AMPA receptors in the DLS play a role in the modulation of binge-like alcohol drinking. These findings further validate the importance of the DLS for alcohol related behaviors and alcohol use disorder.
背外侧纹状体（DLS）参与成瘾、奖励和与酒精相关的行为。DLS 主要接收兴奋性输入，这些输入由突触后 AMPA 受体门控。我们拮抗 DLS 中的 AMPA 受体，以研究这种调节如何影响雄性和雌性 C57BL/6J 小鼠的 binge 样饮酒行为，以及与之相关的饮酒史是否改变背内侧纹状体（DMS）和 DLS 的 AMPA 受体表达。我们还研究了 DLS 内 NBQX 对小鼠运动活动和蔗糖饮用的影响。小鼠每天有两小时的自由接触 20%酒精，共七天。第七天，小鼠在接触酒精前接受 DLS 内四种 NBQX（盐水、0.15、0.5 或 1.5μg/侧）浓度之一的输注，一种 AMPA 受体拮抗剂。测定两小时 binge 酒精摄入量、运动活动和血液酒精浓度。DLS 内 NBQX 以 U 形方式减少雄性和雌性小鼠 binge 样饮酒。摄入量预测血液酒精浓度，而运动活动不受影响。在后续实验中，我们评估了减少酒精摄入量最有效的 NBQX 浓度是否也减少了蔗糖饮用，发现 DLS 内 NBQX 没有改变雄性和雌性小鼠的蔗糖饮用。这些数据表明 DLS 中的 AMPA 受体在调节 binge 样饮酒中起作用。这些发现进一步验证了 DLS 在与酒精相关的行为和酒精使用障碍中的重要性。
