Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP), São Paulo, Brazil.
Ophidiarium LNN-FMRP-USP/INeC, Ribeirão Preto School of Medicine of the University of São Paulo (FMRP-USP), São Paulo, Brazil.
Acta Neurobiol Exp (Wars). 2020;80(2):179-191.
The purpose of this study was to investigate whether the panicolytic‑like effect of different doses of anandamide microinjected into the anterior hypothalamus (AH) follows the same pattern of a bell‑shaped dose‑response curve observed with the same dose treatment in dorsomedial and ventromedial hypothalamus. We investigated this assumption by administering the cannabinoid and vanilloid receptor agonist anandamide into the anterior hypothalamus of mice and exposing them to the real threatening situation by using our experimental model based on confrontations between rodents and wild snakes. Our findings showed a gradual decay of response, with a significant attenuation of the panic attack‑like responses with anandamide at the highest dose but no effect was found after anandamide at the lowest or intermediate doses. An immunohistochemical procedure showed a lower degree of TRPV1 receptor and moderate to higher degree of Cb1 receptors in anterior hypothalamus. In conclusion, the pattern of dose‑response curve of anandamide microinjected in the AH does not seem to be the same classical pattern compared with other hypothalamic nuclei.
本研究旨在探讨不同剂量的花生四烯酸酰胺（anandamide）在前脑垂体（anterior hypothalamus，AH）中微注射是否遵循与在背内侧核（dorsomedial hypothalamus，DMH）和腹内侧核（ventromedial hypothalamus，VMH）中相同剂量处理所观察到的钟形剂量反应曲线相同的惊恐样效应模式。我们通过向小鼠的前脑垂体注射大麻素和香草素受体激动剂花生四烯酸酰胺，并使用基于啮齿动物与野生蛇类对抗的实验模型，将它们暴露在真正的威胁情境中，从而验证了这一假设。我们的研究结果表明，反应逐渐减弱，在最高剂量下，花生四烯酸酰胺引起的惊恐样反应明显减弱，但在最低或中间剂量下没有效果。免疫组织化学程序显示，前脑垂体中的 TRPV1 受体程度较低，而 Cb1 受体程度则适中或较高。总之，与其他下丘脑核相比，在前脑垂体中注射花生四烯酸酰胺的剂量反应曲线模式似乎并不相同。
