Vergara Macarena D, Keller Victor N, Fuentealba José A, Gysling Katia
Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
Department of Pharmacy, Faculty of Chemistry, Pontificia Universidad Católica de Chile, Santiago, Chile.
Behav Brain Res. 2017 May 1;324:130-137. doi: 10.1016/j.bbr.2017.01.050. Epub 2017 Feb 16.
The prelimbic area (PL) of the medial Prefrontal cortex (mPFC) is involved in the acquisition and expression of conditioned and innate fear. Both types of fear share several neuronal pathways. It has been documented that dopamine (DA) plays an important role in the regulation of aversive memories in the mPFC. The exposure to an aversive stimulus, such as the smell of a predator odor or the exposure to footshock stress is accompanied by an increase in mPFC DA release. Evidence suggests that the type 4 dopaminergic receptor (D4R) is the molecular target through which DA modulates fear expression. In fact, the mPFC is the brain region with the highest expression of D4R; however, the role of D4R in the expression of innate fear has not been fully elucidated. Therefore, the principal objective of this work was to evaluate the participation of mPFC D4R in the expression of innate fear. Rats were exposed to the elevated plus-maze (EPM) and to the cat odor paradigm after the intra PL injection of L-745,870, selective D4R antagonist, to measure the expression of fear-related behaviors. Intra PL injection of L-745,870 increased the time spent in the EPM open arms and decreased freezing behavior in the cat odor paradigm. Our results also showed that D4R is expressed in GABAergic and pyramidal neurons in the PL region of PFC. Thus, D4R antagonism in the PL decreases the expression of innate fear-behavior indicating that the activation of D4R in the PL is necessary for the expression of innate fear-behavior.
内侧前额叶皮质（mPFC）的前边缘区（PL）参与条件性恐惧和先天性恐惧的习得与表达。这两种恐惧类型共享若干神经元通路。有文献记载，多巴胺（DA）在mPFC厌恶记忆的调节中起重要作用。暴露于厌恶刺激，如捕食者气味或足部电击应激，会伴随着mPFC中DA释放的增加。证据表明，4型多巴胺能受体（D4R）是DA调节恐惧表达的分子靶点。事实上，mPFC是D4R表达最高的脑区；然而，D4R在先天性恐惧表达中的作用尚未完全阐明。因此，本研究的主要目的是评估mPFC D4R在先天性恐惧表达中的作用。在PL内注射选择性D4R拮抗剂L-745,870后，将大鼠暴露于高架十字迷宫（EPM）和猫气味范式中，以测量恐惧相关行为的表达。PL内注射L-745,870增加了大鼠在EPM开放臂中停留的时间，并减少了在猫气味范式中的僵立行为。我们的结果还表明，D4R在PFC的PL区域的GABA能神经元和锥体神经元中表达。因此，PL中的D4R拮抗作用降低了先天性恐惧行为的表达，表明PL中D4R的激活是先天性恐惧行为表达所必需的。
