Laboratory of Pharmacology, Department of Drugs and Medicines, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil; Joint UFSCar-UNESP Graduate Program in Physiological Sciences, Brazil.
Laboratory of Pharmacology, Department of Drugs and Medicines, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil.
Brain Res Bull. 2022 Apr;181:175-182. doi: 10.1016/j.brainresbull.2022.02.001. Epub 2022 Feb 3.
Previous studies showed a prominent role of the medial prefrontal cortex (mPFC), especially the prelimbic (PL) and infralimbic (IL) subregions, in behavioral and physiological responses to stressful stimuli. Nevertheless, the local neurochemical mechanisms involved are not completely understood. In this sense, previous studies identified cholinergic terminals within the mPFC, and stressful stimuli increased local acetylcholine release. Despite these pieces of evidence, the specific role of cholinergic neurotransmission in different subregions of the mPFC controlling the cardiovascular responses to stress has never been systematically evaluated. Therefore, the purpose of this study was to investigate the involvement of cholinergic neurotransmission present within PL and IL in cardiovascular responses to an acute session of restraint stress in rats. For this, rats received bilateral microinjection of the choline uptake inhibitor hemicholinium-3 before exposure to restraint stress. The arterial pressure and heart rate (HR) increases and the decrease in tail skin temperature as an indirect measurement of sympathetically-mediated cutaneous vasoconstriction were recorded throughout the restraint stress session. The results showed that the depletion of acetylcholine within the PL caused by local microinjection of hemicholinium-3 decreased the tachycardia to restraint stress, but without affecting the pressor response and the drop in tail skin temperature. Conversely, IL treatment with hemicholinium-3 decreased the restraint-evoked pressor response and the sympathetically-mediated cutaneous vasoconstriction without interfering with the HR response. Taken together, these results indicate functional differences of cholinergic neurotransmission within the PL and IL in control of cardiovascular and autonomic responses to stressful stimuli.
先前的研究表明，内侧前额叶皮层（mPFC），特别是额前皮质（PL）和下边缘皮质（IL）亚区，在对应激刺激的行为和生理反应中起着重要作用。然而，涉及的局部神经化学机制尚不完全清楚。在这方面，先前的研究确定了 mPFC 内的胆碱能末梢，应激刺激增加了局部乙酰胆碱的释放。尽管有这些证据，但胆碱能神经传递在控制应激心血管反应的 mPFC 不同亚区中的特定作用从未得到系统评估。因此，本研究的目的是调查 PL 和 IL 内的胆碱能神经传递在大鼠急性束缚应激心血管反应中的作用。为此，大鼠在暴露于束缚应激之前接受双侧微注射胆碱摄取抑制剂 hemicholinium-3。整个束缚应激过程中记录动脉压和心率（HR）的增加以及尾部皮肤温度的下降，作为交感神经介导的皮肤血管收缩的间接测量。结果表明，hemicholinium-3 局部微注射导致 PL 内乙酰胆碱耗竭，降低了束缚应激时的心动过速，但不影响升压反应和尾部皮肤温度下降。相反，IL 用 hemicholinium-3 处理降低了束缚诱发的升压反应和交感神经介导的皮肤血管收缩，而不干扰 HR 反应。综上所述，这些结果表明，PL 和 IL 内的胆碱能神经传递在控制心血管和自主神经对应激刺激的反应方面存在功能差异。
