Opioid neurotransmission modulates defensive behavior and fear-induced antinociception in dangerous environments

•Naloxone causes anxiolytic-like effect and decreases anxiety-induced antinociception in EPM test.•Naloxone has no effect on escape/avoidance responses, but decreases fear-induced antinociception in ETM test.•Naloxone decreases anxiety- and panic attack-like behaviors in rattlesnake-threatened preys.•Naloxone decreases unconditioned fear-induced antinociception in threatened rodents.

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 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.

Graphical abstractPanic attack-like behavioral responses displayed by Wistar rats threatened by Crotalus durissus terrificus (Reptilia, Viperidae) wild venomous snakes are reverted to fearlessness by the peripheral treatment with naloxone. Background: Photomicrograph of a transverse section of the dorsal midbrain of a Wistar rat showing a fast blue neurotracer-labeled neuron situated in the dorsolateral column of the periaqueductal gray matter, which is rich in opioid peptide neurons and receptors.Download high-res image (161KB)Download full-size image