Department of Psychiatry, McGill University, 1033 Pine Avenue West, Montreal, H3A 1A1, Quebec, Canada.
Department of Neurology and Neurosurgery, McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, 3801 University St., Montreal, H3A 2B4, Quebec, Canada.
Sci Rep. 2020 May 6;10(1):7627. doi: 10.1038/s41598-020-63977-7.
When a cue no longer predicts a threat, a diminished ability to extinguish or reverse this association is thought to increase risk for stress-related disorders. Despite the clear clinical relevance, the mediating neurochemical mechanisms of threat reversal have received relatively little study. One neurotransmitter implicated in rodent research of changing associations with threat is dopamine. To study whether dopamine is involved in threat reversal in humans, we used high-resolution positron emission tomography (PET) coupled with F-fallypride. Twelve healthy volunteers (6 F/6 M) underwent three PET scans: (i) at baseline, (ii) following threat conditioning (the response to a cue associated with electric wrist shock), and (iii) following threat reversal (the response to the same cue now associated with safety). We observed moderate evidence of reduced dopamine D2/3 receptor availability, consistent with greater dopamine release, in the bilateral anterior hippocampus following threat reversal, in response to a safety cue that was previously associated with threat, as compared to both baseline and during exposure to the same cue prior to threat reversal. These findings offer the first preliminary evidence that the response to a previously threatening cue that has since become associated with safety involves dopaminergic neurotransmission within the hippocampus in healthy humans.
当线索不再预测威胁时，人们认为这种消除或反转这种关联的能力下降会增加与压力相关的障碍的风险。尽管这在临床上具有明显的相关性，但威胁反转的中介神经化学机制的研究相对较少。在涉及改变与威胁相关的关联的啮齿动物研究中，一种涉及的神经递质是多巴胺。为了研究多巴胺是否参与人类的威胁反转，我们使用了高分辨率正电子发射断层扫描（PET）结合 F-氟丙嗪。12 名健康志愿者（6 名女性和 6 名男性）接受了三次 PET 扫描：（i）在基线时，（ii）在威胁条件作用后（对与电击腕部相关的线索的反应），以及（iii）在威胁反转后（对与安全相关的相同线索的反应）。我们观察到，在威胁反转后，双侧前海马体中的多巴胺 D2/3 受体可用性减少，这与在先前与威胁相关的安全线索的反应中观察到的多巴胺释放增加有关，与基线和在威胁反转前暴露于相同线索时相比。这些发现提供了初步证据，表明对先前威胁性线索的反应，即现在与安全相关，涉及健康人类中海马体内的多巴胺能神经传递。
