PDF(Pubmed)
Abstract：
UNASSIGNED: Alcohol use disorder (AUD) is commonly associated with anxiety disorders and enhanced stress-sensitivity; symptoms that can worsen during withdrawal to perpetuate continued alcohol use. Alcohol increases neuroimmune activity in the brain. Our recent evidence indicates that alcohol directly modulates neuroimmune function in the central amygdala (CeA), a key brain region regulating anxiety and alcohol intake, to alter neurotransmitter signaling. We hypothesized that cannabinoids, such as cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC), which are thought to reduce neuroinflammation and anxiety, may have potential utility to alleviate alcohol withdrawal-induced stress-sensitivity and anxiety-like behaviors via modulation of CeA neuroimmune function.
UNASSIGNED: We tested the effects of CBD and CBD:THC (3:1 ratio) on anxiety-like behaviors and neuroimmune function in the CeA of mice undergoing acute (4-h) and short-term (24-h) withdrawal from chronic intermittent alcohol vapor exposure (CIE). We further examined the impact of CBD and CBD:THC on alcohol withdrawal behaviors in the presence of an additional stressor.
UNASSIGNED: We found that CBD and 3:1 CBD:THC increased anxiety-like behaviors at 4-h withdrawal. At 24-h withdrawal, CBD alone reduced anxiety-like behaviors while CBD:THC had mixed effects, showing increased center time indicating reduced anxiety-like behaviors, but increased immobility time that may indicate increased anxiety-like behaviors. These mixed effects may be due to altered metabolism of CBD and THC during alcohol withdrawal. Immunohistochemical analysis showed decreased S100β and Iba1 cell counts in the CeA at 4-h withdrawal, but not at 24-h withdrawal, with CBD and CBD:THC reversing alcohol withdrawal effects..
UNASSIGNED: These results suggest that the use of cannabinoids during alcohol withdrawal may lead to exacerbated anxiety depending on timing of use, which may be related to neuroimmune cell function in the CeA.
UNASSIGNED: We tested the effects of CBD and CBD:THC (3:1 ratio) on anxiety-like behaviors and neuroimmune function in the CeA of mice undergoing acute (4-h) and short-term (24-h) withdrawal from chronic intermittent alcohol vapor exposure (CIE). We further examined the impact of CBD and CBD:THC on alcohol withdrawal behaviors in the presence of an additional stressor.
UNASSIGNED: We found that CBD and 3:1 CBD:THC increased anxiety-like behaviors at 4-h withdrawal. At 24-h withdrawal, CBD alone reduced anxiety-like behaviors while CBD:THC had mixed effects, showing increased center time indicating reduced anxiety-like behaviors, but increased immobility time that may indicate increased anxiety-like behaviors. These mixed effects may be due to altered metabolism of CBD and THC during alcohol withdrawal. Immunohistochemical analysis showed decreased S100β and Iba1 cell counts in the CeA at 4-h withdrawal, but not at 24-h withdrawal, with CBD and CBD:THC reversing alcohol withdrawal effects..
UNASSIGNED: These results suggest that the use of cannabinoids during alcohol withdrawal may lead to exacerbated anxiety depending on timing of use, which may be related to neuroimmune cell function in the CeA.
摘要：
■酒精使用障碍（AUD）通常与焦虑症和增强的压力敏感性有关；在戒断期间症状可能会恶化，从而使持续使用酒精。酒精会增加大脑中的神经免疫活动。我们最近的证据表明，酒精直接调节中央杏仁核（CeA）的神经免疫功能，调节焦虑和酒精摄入的关键大脑区域，改变神经递质信号。我们假设大麻素，如大麻二酚(CBD)和Δ9-四氢大麻酚(THC)，被认为可以减少神经炎症和焦虑，可能通过调节CeA神经免疫功能来减轻酒精戒断引起的压力敏感性和焦虑样行为。
■我们测试了CBD和CBD：THC（3：1比例）对经历急性（4小时）和短期（24小时）慢性间歇性酒精蒸气暴露（CIE）的小鼠CeA的焦虑样行为和神经免疫功能的影响。我们进一步检查了CBD和CBD：THC在存在其他压力源的情况下对酒精戒断行为的影响。
■我们发现CBD和3：1CBD：THC在4小时戒断时会增加焦虑样行为。在24小时退出时，单独的CBD减少了焦虑样行为，而CBD：THC具有混合效应，显示中心时间增加，表明焦虑样行为减少，但不动时间增加可能表明焦虑样行为增加。这些混合效应可能是由于酒精戒断期间CBD和THC的代谢改变。免疫组织化学分析显示，在戒断4小时时，CeA中的S100β和Iba1细胞计数降低，但不是在24小时内退出，与CBD和CBD：THC逆转酒精戒断效应。.
■这些结果表明，戒酒期间使用大麻素可能会导致焦虑加剧，具体取决于使用时机，这可能与CeA中的神经免疫细胞功能有关。
■我们测试了CBD和CBD：THC（3：1比例）对经历急性（4小时）和短期（24小时）慢性间歇性酒精蒸气暴露（CIE）的小鼠CeA的焦虑样行为和神经免疫功能的影响。我们进一步检查了CBD和CBD：THC在存在其他压力源的情况下对酒精戒断行为的影响。
■我们发现CBD和3：1CBD：THC在4小时戒断时会增加焦虑样行为。在24小时退出时，单独的CBD减少了焦虑样行为，而CBD：THC具有混合效应，显示中心时间增加，表明焦虑样行为减少，但不动时间增加可能表明焦虑样行为增加。这些混合效应可能是由于酒精戒断期间CBD和THC的代谢改变。免疫组织化学分析显示，在戒断4小时时，CeA中的S100β和Iba1细胞计数降低，但不是在24小时内退出，与CBD和CBD：THC逆转酒精戒断效应。.
■这些结果表明，戒酒期间使用大麻素可能会导致焦虑加剧，具体取决于使用时机，这可能与CeA中的神经免疫细胞功能有关。
