Traumatic brain injury (TBI) affects approximately 3 million Americans yearly and increases vulnerability to developing psychiatric comorbidities. Alcohol use disorder (AUD) is the most prevalent psychiatric diagnosis preceding injury and TBI may increase subsequent alcohol use. The basolateral amygdala (BLA) is a limbic structure commonly affected by TBI that is implicated in anxiety and AUD. Endocannabinoids (eCBs) regulate synaptic activity in the BLA, and BLA eCB modulation alters anxiety-like behavior and stress reactivity. Previous work from our laboratories showed that systemic eCB degradation inhibition ameliorates TBI-induced increases in anxiety-like behavior and motivation to respond for alcohol in male rats. Here, we used a lateral fluid percussion model to test moderate TBI effects on anxiety-like behavior, alcohol drinking, and eCB levels and cell signaling in BLA, as well as the effect of alcohol drinking on anxiety-like behavior and the BLA eCB system, in female rats. Our results show that TBI does not promote escalation of operant alcohol self-administration or increase anxiety-like behavior in female rats. In the BLA, TBI and alcohol drinking alter tissue amounts of 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (anandamide; AEA) 1 h post-injury, and 2-AG levels remain low 11 days post-injury. Eleven days after injury, BLA pyramidal neurons were hyperexcitable, but measures of synaptic transmission and eCB signaling were unchanged. These data show that TBI impacts BLA 2-AG tissue levels, that this effect is modified by alcohol drinking, and also that TBI increases BLA cell excitability.

中文翻译：

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外伤性脑损伤和饮酒改变雌性大鼠基底外侧杏仁核内源性大麻素

创伤性脑损伤 (TBI) 每年影响大约 300 万美国人，并增加了对发展中的精神疾病的脆弱性。酒精使用障碍 (AUD) 是受伤前最普遍的精神病学诊断，TBI 可能会增加随后的酒精使用。基底外侧杏仁核 (BLA) 是一种边缘结构，通常受 TBI 影响，与焦虑和 AUD 有关。内源性大麻素 (eCBs) 调节 BLA 中的突触活动，而 BLA eCB 调节改变焦虑样行为和压力反应性。我们实验室以前的工作表明，全身性 eCB 降解抑制可改善 TBI 诱导的雄性大鼠焦虑样行为和对酒精的反应动机的增加。在这里，我们使用横向流体冲击模型来测试中度 TBI 对焦虑样行为、饮酒、BLA 中的 eCB 水平和细胞信号传导，以及饮酒对雌性大鼠焦虑样行为和 BLA eCB 系统的影响。我们的研究结果表明，TBI 不会促进操作性酒精自我管理的升级或增加雌性大鼠的焦虑样行为。在 BLA 中，TBI 和饮酒会改变组织中 2-花生四烯酸甘油 (2-AG) 和N-花生四烯酰乙醇胺（anandamide；AEA）在受伤后 1 小时，2-AG 水平在受伤后 11 天仍然很低。受伤 11 天后，BLA 锥体神经元过度兴奋，但突触传递和 eCB 信号传导的测量值没有变化。这些数据表明，TBI 会影响 BLA 2-AG 组织水平，这种影响会因饮酒而改变，而且 TBI 会增加 BLA 细胞的兴奋性。