School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil.
School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil; Joint UFSCar-UNESP Graduate Program in Physiological Sciences, São Carlos, SP, Brazil.
Behav Brain Res. 2021 Jan 15;397:112947. doi: 10.1016/j.bbr.2020.112947. Epub 2020 Oct 1.
The brain renin-angiotensin system (RAS) has been implicated in anxiety and depression disorders, but the specific brain sites involved are poorly understood. The medial amygdaloid nucleus (MeA) is involved in expression of behavioral responses. However, despite evidence of the presence of all angiotensinergic receptors in this amygdaloid nucleus, regulation of anxiety- and depressive-like behaviors by angiotensinergic neurotransmissions within the MeA has never been reported. Thus, the present study aimed to investigate the role angiotensin II (AT and AT receptors) and angiotensin-(1-7) (Mas receptor) receptors present within the MeA in behavioral responses in the elevated plus-maze (EPM) and forced swimming test (FST). For this, male Wistar rats had cannula-guide bilaterally implanted into the MeA, and independent sets of animals received bilateral microinjections of either the selective AT receptor antagonist losartan, the selective AT receptor antagonist PD123319, the selective Mas receptor antagonist A-779 or vehicle into the MeA before the EPM and FST. Treatment of the MeA with either PD123319 or A-779 decreased the EPM open arms exploration, while losartan did not affect behavioral responses in this apparatus. However, intra-MeA microinjection of losartan decreased immobility in the FST. Administration of either PD123319 or A-779 into the MeA did not affect the immobility during the FST, but changed the pattern of the active behaviors swimming and climbing. Altogether, these results indicate the presence of different angiotensinergic mechanisms within the MeA controlling behavioral responses in the FST and EPM.
大脑肾素-血管紧张素系统(RAS)与焦虑和抑郁障碍有关,但涉及的特定脑区知之甚少。 杏仁中央核(MeA)参与行为反应的表达。 然而,尽管该杏仁核中存在所有血管紧张素能受体的证据,但血管紧张素能神经传递在 MeA 内对焦虑和抑郁样行为的调节尚未被报道。 因此,本研究旨在研究 MeA 内的血管紧张素 II(AT 和 AT 受体)和血管紧张素-(1-7)(Mas 受体)受体在高架十字迷宫(EPM)和强迫游泳试验(FST)中的行为反应中的作用。 为此,雄性 Wistar 大鼠双侧植入 MeA 引导的套管,并将独立的动物组分别接受双侧微量注射选择性 AT 受体拮抗剂 losartan、选择性 AT 受体拮抗剂 PD123319、选择性 Mas 受体拮抗剂 A-779 或载体进入 MeA,然后进行 EPM 和 FST。 MeA 内给予 PD123319 或 A-779 可减少 EPM 开放臂探索,而 losartan 对该仪器中的行为反应没有影响。 然而,MeA 内微注射 losartan 可减少 FST 中的不动性。 向 MeA 内给予 PD123319 或 A-779 不会影响 FST 期间的不动性,但会改变游泳和攀爬的活动行为模式。 总之,这些结果表明 MeA 内存在不同的血管紧张素能机制,可控制 FST 和 EPM 中的行为反应。