Laboratory of Pharmacology, São Paulo State University (UNESP), School of Pharmaceutical Sciences, Araraquara, SP, Brazil; Joint UFSCar-UNESP Graduate Program in Physiological Sciences, São Carlos, SP, Brazil.
Laboratory of Pharmacology, São Paulo State University (UNESP), School of Pharmaceutical Sciences, Araraquara, SP, Brazil; Joint UFSCar-UNESP Graduate Program in Physiological Sciences, São Carlos, SP, Brazil.
Brain Res Bull. 2021 Jan;166:102-109. doi: 10.1016/j.brainresbull.2020.11.010. Epub 2020 Nov 20.
The lateral hypothalamus (LH) is implicated in the physiological and behavioral responses during stressful events. However, the local neurochemical mechanisms related to control of stress responses by this hypothalamic area are not completely understood. Therefore, in this study we evaluated the involvement of CRFergic neurotransmission acting through the CRF receptor within the LH in cardiovascular responses evoked by an acute session of restraint stress in rats. For this, we investigated the effect of bilateral microinjection of different doses (0.01, 0.1 and 1 nmol/100 nL) of the selective CRF receptor antagonist CP376395 into the LH on arterial pressure and heart rate increases and decrease in tail skin temperature evoked by acute restraint stress. We found that all doses of the CRF receptor antagonist microinjected into the LH decreased the restraint-evoked tachycardia, but without affecting the arterial pressure and tail skin temperature responses. Additionally, treatment of the LH with CP376395 at the doses of 0.1 and 1 nmol/100 nL increased the basal values of both heart rate and arterial pressure, whereas the dose of 0.1 nmol/100 nL decreased the skin temperature. Taken together, these findings indicate that CRFergic neurotransmission in the LH, acting through activation of local CRF receptors, plays a facilitatory role in the tachycardia observed during aversive threats, but without affecting the pressor and tail skin temperature responses. Our results also provide evidence that LH CRFergic neurotransmission in involved in tonic maintenance of cardiovascular function.
外侧下丘脑(LH)参与应激事件期间的生理和行为反应。然而,与该下丘脑区域控制应激反应相关的局部神经化学机制尚不完全清楚。因此,在这项研究中,我们评估了 LH 内通过 CRF 受体作用的 CRF 能神经传递在大鼠急性束缚应激引起的心血管反应中的作用。为此,我们研究了将不同剂量(0.01、0.1 和 1 nmol/100 nL)的选择性 CRF 受体拮抗剂 CP376395 双侧微注射到 LH 对急性束缚应激引起的动脉压和心率增加以及尾部皮肤温度降低的影响。我们发现,LH 内注射 CRF 受体拮抗剂的所有剂量均降低了束缚引起的心动过速,但不影响动脉压和尾部皮肤温度反应。此外,CP376395 以 0.1 和 1 nmol/100 nL 的剂量处理 LH 增加了心率和动脉压的基础值,而 0.1 nmol/100 nL 的剂量降低了皮肤温度。综上所述,这些发现表明,LH 中的 CRF 能神经传递通过激活局部 CRF 受体,在厌恶威胁期间观察到的心动过速中起促进作用,但不影响升压和尾部皮肤温度反应。我们的结果还提供了证据,表明 LH 中的 CRF 能神经传递参与心血管功能的紧张维持。