4.5 Article

OPIOID NEUROTRANSMISSION MODULATES DEFENSIVE BEHAVIOR AND FEAR-INDUCED ANTINOCICEPTION IN DANGEROUS ENVIRONMENTS

Journal

NEUROSCIENCE
Volume 354, Issue -, Pages 178-195

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2017.04.032

Keywords

innate fear; conditioned fear/anticipatory anxiety; panic attacks; endogenous opioid peptide-mediated neural system; prey-versus-rattlesnake pit viper paradigm; instinctive fear-induced antinociception

Categories

Funding

  1. Conselho Nacional de Pesquisa e Desenvolvimento Tecnologico (CNPq, Brazil) [470119/2004-7]
  2. Fundacao de Apoio ao Ensino, Pesquisa e Assistencia do HC-FMRP-USP (FAEPA, Brazil) [1291/97, 355/2000, 68/2001, 15/2003]
  3. Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Brazil) [03/07202-6, 03/01768-8, 03/01794-9, 07/01174-1, 2012/03798-0]
  4. Pro-Rectory of the University of Sao Paulo (USP) Research grant (IaPQ) [NAP-USP-NuPNE-156]
  5. FAPESP [03/01768-8, 02/13307-2, 04/10173-0, 2012/22681-7, 02/01497-1]
  6. CNPq [301905/2010-0, 200629/2005-0, 057/2005, 04/2008-AT, 501858/2005-9, 500896/2008-9]
  7. Clinical Neurology (FMRIB Centre) Department of the University of Oxford, England, United Kingdom
  8. Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [12/03798-0] Funding Source: FAPESP

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The effects of endogenous opioid peptide antagonists on panic-related responses are controversial. Using elevated mazes and a prey-versus-predator paradigm, we investigated the involvement of the endogenous opioid peptide-mediated system in the modulation of anxiety- and panic attack-induced responses and innate fear-induced antinociception in the present work. Wistar rats were intraperitoneally pretreated with either physiological saline or naloxone at different doses and were subjected to either the elevated plus- or T-maze test or confronted by Crotalus durissus terrificus. The defensive behaviors of the rats were recorded in the presence of the predator and at 24 h after the confrontation, when the animals were placed in the experimental enclosure without the rattlesnake. The peripheral non-specific blockade of opioid receptors had a clear anxiolytic-like effect on the rats subjected to the elevated plus-maze but not on those subjected to the elevated T-maze; however, a clear panicolytic-like effect was observed, i.e., the defensive behaviors decreased, and the preyversus-predator interaction responses evoked by the presence of the rattlesnakes increased. A similar effect was noted when the rats were exposed to the experimental context in the absence of the venomous snake. After completing all tests, the naloxone-treated groups exhibited less anxiety/fear-induced antinociception than the control group, as measured by the tail-flick test. These findings demonstrate the anxiolytic and panicolytic-like effects of opioid receptor blockade. In addition, the fearlessness behavior displayed by preys treated with naloxone at higher doses enhanced the defensive behavioral responses of venomous snakes. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

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