• Norberto Cysne Coimbra, Fabrício Calvo, Rafael Carvalho Almada, Renato Leonardo Freitas, Tatiana Paschoalin-Maurin, Tayllon Dos Anjos-Garcia, Daoud Hibrahim Elias-Filho, Walter Adriano Ubiali, Bruno Lobão-Soares, and Irene Tracey.
• Pain Imaging Neuroscience Group, Department of Physiology, Anatomy & Genetics, University of Oxford, South Parks Road, Oxford OX1 3OX, United Kingdom; FMRIB Centre, Department of Clinical Neurology of the University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom; Laboratory of Neuroanatomy & Neuropsychobiology, Department of Pharmacology, School of Medicine of Ribeirão Preto of the University of São Paulo (FMRP-USP), Av. Bandeirantes, 3900, 14049-900 Ribeirão Preto, São Paulo, Brazil; NAP-USP-Neurobiology of Emotions Research Centre (NuPNE), Ribeirão Preto Medical School of the University of São Paulo, Av Bandeirantes, 3900, Ribeirão Preto, São Paulo 14049-900, Brazil. Electronic address: ncoimbr@fmrp.usp.br.
• Neuroscience. 2017 Jun 23; 354: 178-195.

AbstractThe 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 24h 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 prey-versus-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.Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

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