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CRF modulation of central monoaminergic function: Implications for sex differences in alcohol drinking and anxiety

机译：CRF调制中枢单氨基能函数：对酒精饮酒和焦虑的性别差异的影响

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Decades of research have described the importance of corticotropin-releasing factor (CRF) signaling in alcohol addiction, as well as in commonly co-expressed neuropsychiatric diseases, including anxiety and mood disorders. However, CRF signaling can also acutely regulate binge alcohol consumption, anxiety, and affect in non-dependent animals, possibly via modulation of central monoaminergic signaling. We hypothesize that basal CRF tone is particularly high in animals and humans with an inherent propensity for high anxiety and alcohol consumption, and thus these individuals are at increased risk for the development of alcohol use disorder and comorbid neuropsychiatric diseases. The current review focuses on extrahypothalamic CRF circuits, particularly those stemming from the bed nucleus of the stria terminalis (BNST), found to play a role in basal phenotypes, and examines whether the intrinsic hyperactivity of these circuits is sufficient to escalate the expression of these behaviors and steepen the trajectory of development of disease states. We focus our efforts on describing CRF modulation of biogenic amine neuron populations that have widespread projections to the forebrain to modulate behaviors, including alcohol and drug intake, stress reactivity, and anxiety. Further, we review the known sex differences and estradiol modulation of these neuron populations and CRF signaling at their synapses to address the question of whether females are more susceptible to the development of comorbid addiction and stress-related neuropsychiatric diseases because of hyperactive extrahypothalamic CRF circuits compared to males.
机译：几十年的研究已经描述了皮质激素释放因子（CRF）信号传导在酒精成瘾中的重要性，以及通常共同表达的神经精神疾病，包括焦虑和情绪障碍。然而，CRF信号传导也可以敏锐地调节狂犬醇消费，焦虑，并影响非依赖性动物，可能通过调节中枢单氨基能信号传导。我们假设动物和人类的基础CRF音调特别高，具有高焦虑和酒精消费的固有倾向，因此这些个体在增加酒精使用障碍和可血管性神经精神疾病的风险增加。目前的审查重点介绍了额外的CRF电路，特别是那些源于斯特拉毒性的床核（BNST），发现在基础表型中发挥作用，并检查这些电路的内在多动性是否足以升级这些电路的表达式行为和陡峭的疾病状态发展的轨迹。我们专注于描述生物胺神经元种群的CRF调节，这些胺神经元种群具有广泛的预测来调节行为，包括酒精和药物摄入，应激反应性和焦虑。此外，我们在其突触中审查了这些神经元种群的已知性差异和雌二醇调节，并在其突触处解决了女性更容易发育合并性成瘾和相关的神经精神疾病的问题，因为相比过度活跃的脱象CRF电路对男性。

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