Department of Neurobiology and Anatomy, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA.
Neuroscience. 2020 Sep 1;443:84-92. doi: 10.1016/j.neuroscience.2020.07.024. Epub 2020 Jul 21.
The relationship between stress and alcohol-drinking behaviors has been intensively explored; however, neuronal substrates and neurotransmitter dynamics responsible for a causal link between these conditions are still unclear. Here, we optogenetically manipulated locus coeruleus (LC) norepinephrine (NE) activity by applying distinct stimulation protocols in order to explore how phasic and tonic NE release dynamics control alcohol-drinking behaviors. Our results clearly demonstrate contrasting behavioral consequences of LC-NE circuitry activation during low and high frequency stimulation. Specifically, applying tonic stimulation during a standard operant drinking session resulted in increased intake, while phasic stimulation decreased this measure. Furthermore, stimulation during extinction probe trials, when the lever press response was not reinforced, did not significantly alter alcohol-seeking behavior if a tonic pattern was applied. However, phasic stimulation substantially suppressed the number of lever presses, indicating decreased alcohol seeking under the same experimental condition. Given the well-established correlative link between stress and increased alcohol consumption, here we provide the first evidence that tonic LC-NE activity plays a causal role in stress-associated increases in drinking.
压力与饮酒行为之间的关系已经得到了深入探讨；然而，导致这些情况之间存在因果关系的神经元基质和神经递质动力学仍然不清楚。在这里，我们通过应用不同的刺激方案来光遗传操纵蓝斑（LC）去甲肾上腺素（NE）活动，以探索相位和紧张 NE 释放动力学如何控制饮酒行为。我们的结果清楚地表明，在低频和高频刺激期间，LC-NE 回路激活具有截然不同的行为后果。具体来说，在标准操作饮酒会议期间施加紧张刺激会导致摄入量增加，而相位刺激会降低这一指标。此外，如果应用紧张模式，在消退探针试验期间（当按压杠杆反应没有得到强化时），刺激不会显著改变对酒精的寻求行为。然而，相位刺激显著抑制了杠杆按压次数，表明在相同的实验条件下，对酒精的寻求减少了。鉴于压力与饮酒量增加之间存在明确的相关性，我们在这里提供了第一个证据，表明紧张的 LC-NE 活动在与压力相关的饮酒增加中起因果作用。
