Laboratório de Neuroanatomia & Neuropsicobiologia, Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, Av dos Bandeirantes, 3900 Ribeirão Preto, São Paulo 14049-900, Brazil.
Eur J Pharmacol. 2013 Jan 5;698(1-3):235-45. doi: 10.1016/j.ejphar.2012.07.038.
The chemical neuroanatomy and the effects of central administration of opioid antagonists on the innate fear-induced responses elicited by electrical (at escape behaviour threshold) stimulation of the midbrain tectum were determined. The aim of the present work was to investigate the interaction between the tecto-nigral endogenous opioid peptide-mediated disinhibitory pathways and nigro-tectal inhibitory links in the control of panic-like behaviour and their organisation in the continuum comprised by the deep layers of the superior colliculus (dlSC) and the dorsolateral columns of the periaqueductal grey matter (dlPAG). Beta-endorphin-labelled neurons and fibres were found in the dorsal midbrain and also in the substantia nigra. Opioid varicose fibres and terminal buttons were widely distributed in PAG columns and in all substantia nigra subdivisions. Microinjections of naltrexone (a non-selective opioid receptor antagonist; 5.0 μg/0.2 μl) or nor-binaltorphimine (a selective κ-opioid receptor antagonist; 5.0 μg/0.2 μl) in the dlSC/dlPAG continuum, in independent groups of animals, induced significant increases in the escape thresholds for midbrain tectum electrical stimulation. The microinjection of naltrexone or nor-binaltorphimine into the SNpr also increased the escape behaviour threshold for electrical stimulation of dlSC/dlPAG. These morphological and neuropharmacological findings support previous evidence from our team for the role played by the interaction between opioidergic and GABAergic mechanisms in the modulation of innate fear-induced responses. The present data offer a neuroanatomical basis for both intratectal axo-axonic/pre-synaptic and tecto-nigral axo-somatic opioid inhibition of GABAergic nigro-tectal neurons that modulate the dorsal midbrain neurons related to the organisation of fear-related emotional responses.
本研究旨在探讨中脑顶盖电刺激诱发的先天恐惧反应中，顶盖-黑质内源性阿片肽介导的抑制性通路与黑质-顶盖抑制性联系之间的相互作用，以及它们在由高级视皮层深层（dlSC）和导水管周围灰质背外侧柱（dlPAG）组成的连续体中的组织方式。在背侧中脑和黑质中发现了β-内啡肽标记神经元和纤维。阿片类物质的曲张纤维和终末扣带广泛分布在 PAG 柱和所有黑质亚区。纳曲酮（一种非选择性阿片受体拮抗剂；5.0μg/0.2μl）或 nor-binaltorphimine（一种选择性 κ-阿片受体拮抗剂；5.0μg/0.2μl）在 dlSC/dlPAG 连续体中的微注射，在独立的动物组中，导致中脑顶盖电刺激的逃避阈值显著增加。纳曲酮或 nor-binaltorphimine 微注射到 SNpr 也增加了 dlSC/dlPAG 电刺激的逃避行为阈值。这些形态和神经药理学发现支持了我们团队之前的证据，即阿片肽和 GABA 能机制之间的相互作用在调节先天恐惧诱导反应中发挥作用。本研究为中脑顶盖内的轴突-轴突/突触前和顶盖-黑质的轴突-体细胞阿片抑制 GABA 能黑质-顶盖神经元提供了神经解剖学基础，这些神经元调节与恐惧相关的情绪反应组织有关的背侧中脑神经元。
