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首页> 外文期刊>The European Journal of Neuroscience >Absence of dopamine D4 receptors results in enhanced reactivity to unconditioned, but not conditioned, fear.
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Absence of dopamine D4 receptors results in enhanced reactivity to unconditioned, but not conditioned, fear.

机译：多巴胺D4受体的缺乏导致对无条件恐惧的反应性增强，但无条件恐惧。

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The prefrontal cortex receives a major dopaminergic input from the ventral tegmental area, which plays an important role in the integration of neuronal signals influencing behavioural responses to stressful environmental stimuli. The dopamine D4 receptor (D4R) is expressed at highest levels in the prefrontal cortex and is the predominant D2-like receptor localized in this brain area. To investigate the functional significance of D4Rs in dopamine-mediated responses we have analysed a strain of mice lacking this receptor subtype (Drd4-/-). Wild-type and Drd4-/- mice were challenged in two different approach/avoidance conflict paradigms: the elevated plus maze and the light/dark preference exploration test. By these behavioural measures Drd4-/- mice showed heightened avoidance to the more fear-provoking areas of each maze as demonstrated by reduced exploration of the open arms of the plus maze and longer latencies to explore the illuminated compartment of the light/dark shuttle box. These exaggerated avoidance behaviours were further enhanced by an additional handling stress but completely prevented by anxiolytic agents such as the benzodiazepine midazolam and ethanol. Although Drd4-/- mice displayed heightened anxiety, they exhibited normal ethanol preference and consumption in a two-bottle choice test. Learned fear responses evaluated by contextual, cued and instrumental fear-conditioning tests showed no difference between wild-type and Drd4-/- mice. Taken together these results indicate that the absence of D4Rs increases avoidance behaviour to unconditioned stimuli and does not impair behavioural reactions to Pavlovian fear-conditioning, suggesting that the D4R could play a key role in the dopaminergic modulation of cortical signals triggered by environmental stimuli.
机译：前额叶皮层从腹侧被盖区接受主要的多巴胺能输入，这在影响影响对压力环境刺激的行为反应的神经元信号的整合中起重要作用。多巴胺D4受体（D4R）在额叶前额叶中最高水平表达，并且是位于该大脑区域的主要D2样受体。为了调查D4Rs在多巴胺介导的反应中的功能意义，我们分析了缺乏该受体亚型（Drd4-/-）的小鼠品系。野生型和Drd4-/-小鼠在两种不同的方法/避免冲突范式中受到挑战：高架迷宫和明/暗偏好探索测试。通过这些行为测量，Drd4-/-小鼠表现出对每个迷宫更容易引起恐惧的区域的回避，这表现为减少对迷宫的张开臂​​的探查和更长的等待时间来探究明/暗穿梭箱的照明舱室。这些过大的回避行为在附加的处理压力下得到了进一步增强，但被苯并二氮杂咪达唑仑和乙醇等抗焦虑剂完全阻止了。尽管Drd4-/-小鼠表现出更高的焦虑感，但在两瓶选择测试中它们表现出正常的乙醇偏爱和消耗。通过上下文，提示和工具性恐惧条件测试评估的学习到的恐惧反应表明，野生型和Drd4-/-小鼠之间没有差异。总之，这些结果表明，D4R的缺失会增加对无条件刺激的回避行为，并且不会削弱对巴甫洛夫恐惧条件的行为反应，这表明D4R可能在环境刺激触发的皮质信号的多巴胺能调制中起关键作用。

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