Doan Tri Huu, Sato Yuma, Matsumoto Masayuki, Koganezawa Tadachika
Department of Physiology, Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
Front Neurosci. 2021 Mar 29;15:655617. doi: 10.3389/fnins.2021.655617. eCollection 2021.
The lateral habenula (LHb) plays essential roles in behavioral responses to stressful events. Stress is tightly linked to autonomic responses such as cardiovascular responses, yet how the LHb regulates these responses is not well understood. To address this issue, we electrically stimulated the LHb in rats, measured its effects on heart rate (HR) and mean arterial pressure (MAP), and investigated the neural circuits that mediate these LHb-induced cardiovascular responses the autonomic nervous system. We observed that stimulation of the LHb induced bradycardia and pressor responses, whereas stimulation of the adjacent areas changed neither the HR nor the MAP. Bilateral vagotomy and administration of a muscarinic receptor antagonist suppressed the LHb stimulation effect on the HR but not on the MAP, whereas administration of a β-adrenoceptor antagonist partly attenuated the effect on the MAP but not on the HR. Thus, the LHb-induced cardiovascular responses of the HR and the MAP were likely caused by activations of the cardiac parasympathetic nerves and the cardiovascular sympathetic nerves, respectively. Furthermore, administration of a non-selective 5-HT receptor antagonist significantly attenuated the LHb stimulation effects on both the MAP and the HR. A 5-HT receptor antagonist also attenuated the LHb stimulation effects. A low dose of a 5-HT receptor antagonist enhanced the LHb stimulation effects, but a high dose of the drug attenuated them. 5-HT and 5-HT receptor antagonists as well as a 5-HT receptor antagonist did not affect the LHb stimulation effects. Taken together, our findings suggest that the LHb regulates autonomic cardiovascular responses at least partly through the serotonergic system, particularly the 5-HT and 5-HT receptors.
外侧缰核（LHb）在对应激事件的行为反应中起重要作用。应激与自主反应紧密相关，如心血管反应，但LHb如何调节这些反应尚不清楚。为解决这一问题，我们对大鼠的LHb进行电刺激，测量其对心率（HR）和平均动脉压（MAP）的影响，并研究介导这些LHb诱导的心血管反应的神经回路——自主神经系统。我们观察到，刺激LHb会引起心动过缓和升压反应，而刺激相邻区域则不会改变HR和MAP。双侧迷走神经切断术和给予毒蕈碱受体拮抗剂可抑制LHb对HR的刺激作用，但对MAP无影响，而给予β-肾上腺素能受体拮抗剂可部分减弱对MAP的作用，但对HR无影响。因此，LHb诱导的HR和MAP心血管反应可能分别是由心脏副交感神经和心血管交感神经的激活引起的。此外，给予非选择性5-HT受体拮抗剂可显著减弱LHb对MAP和HR的刺激作用。一种5-HT受体拮抗剂也减弱了LHb的刺激作用。低剂量的5-HT受体拮抗剂增强了LHb的刺激作用，但高剂量则减弱了这些作用。5-HT、5-HT受体拮抗剂以及一种5-HT受体拮抗剂均不影响LHb的刺激作用。综上所述，我们的研究结果表明，LHb至少部分通过血清素能系统，特别是5-HT和5-HT受体来调节自主心血管反应。
