Dopamine D1-like receptors in the dorsomedial prefrontal cortex regulate contextual fear conditioning
Dopamine D1-like receptors in the dorsomedial prefrontal cortex regulate contextual fear conditioning
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DOI：
10.1007/s00213-018-5162-7
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发表时间：
2019-01
影响因子：
3.4
通讯作者：
C. Stubbendorff;Ed Hale;H. Cassaday;T. Bast;C. Stevenson
中科院分区：
文献类型：
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作者：
C. Stubbendorff;Ed Hale;H. Cassaday;T. Bast;C. Stevenson
多巴胺D1受体（D1R）信号传导参与情境性恐惧条件反射。D1R拮抗剂SCH 23390损害收购的背景下的恐惧时，全身或注入到背侧海马或基底外侧amygdala.ObjectivesWe确定，如果国家的依赖性可能会占背景下的恐惧条件反射系统SCH 23390管理造成的损害。我们还研究了如果背内侧前额叶皮层（dmPFC），神经核（NAc），腹侧海马（VH）参与介导的影响，系统SCH 23390治疗上下文恐惧conditioning.MethodsIn实验1，SCH 23390（0.1毫克/公斤）或车辆前上下文恐惧条件和/或检索。在实验2中，SCH 23390（2.5 μ g/0.5 uL）或媒介物在情境恐惧条件反射之前局部输注到dmPFC、NAc或VH中，并且在无药物的情况下测试提取。冻结被量化为一个衡量的上下文fear.ResultsIn实验1，SCH 23390前条件反射或前两个条件反射和检索减少冻结检索，而SCH 23390只检索前没有效果。在实验2中，SCH 23390注入dmPFC前调节减少冻结在检索，而注入SCH 23390到NAc或VH没有effect.ConclusionsThe实验1的结果证实了以前的研究表明，D1Rs是必要的收购，但不检索的上下文恐惧和排除状态依赖作为这些发现的解释。此外，实验2的结果提供的证据表明，dmPFC也是神经回路的一部分，通过D1R信号调节上下文恐惧条件反射。
RationaleDopamine D1 receptor (D1R) signalling is involved in contextual fear conditioning. The D1R antagonist SCH23390 impairs the acquisition of contextual fear when administered systemically or infused locally into the dorsal hippocampus or basolateral amygdala.ObjectivesWe determined if state dependency may account for the impairment in contextual fear conditioning caused by systemic SCH23390 administration. We also examined if the dorsomedial prefrontal cortex (dmPFC), nucleus accumbens (NAc), and ventral hippocampus (VH) are involved in mediating the effect of systemic SCH23390 treatment on contextual fear conditioning.MethodsIn experiment 1, SCH23390 (0.1 mg/kg) or vehicle was given before contextual fear conditioning and/or retrieval. In experiment 2, SCH23390 (2.5 μg/0.5 uL) or vehicle was infused locally into dmPFC, NAc, or VH before contextual fear conditioning, and retrieval was tested drug-free. Freezing was quantified as a measure of contextual fear.ResultsIn experiment 1, SCH23390 given before conditioning or before both conditioning and retrieval decreased freezing at retrieval, whereas SCH23390 given only before retrieval had no effect. In experiment 2, SCH23390 infused into dmPFC before conditioning decreased freezing at retrieval, while infusion of SCH23390 into NAc or VH had no effect.ConclusionsThe results of experiment 1 confirm those of previous studies indicating that D1Rs are required for the acquisition but not retrieval of contextual fear and rule out state dependency as an explanation for these findings. Moreover, the results of experiment 2 provide evidence that dmPFC is also part of the neural circuitry through which D1R signalling regulates contextual fear conditioning.