The blockade of μ-opioid receptors in the lateral hypothalamus enhances panic attack-like behaviour and diminishes defensive antinociception

Abstract

The lateral hypothalamus (LH) sends neural pathways to structures involved on predator-related defensive behaviours, escape and antinociception. The aim of this study was to investigate the role played by µ-opioid receptors located on LH neurons in defensive behaviour and unconditioned fear-induced antinociception elicited by electric stimulation of LH. To achieve the goals, the µ1-opioid receptor selective antagonist naloxonazine was administered at different concentrations in the LH, and the defensive behaviour and fear-induced antinociception elicited by electrical stimulation of LH were evaluated. The electrical stimulation of LH caused escape behaviour followed by defensive antinociception. Microinjections of naloxonazine in a concentration of 5.0 μg/0.2 μL in the LH decreased the aversive stimulus-induced escape behaviour thresholds, but diminished defensive antinociception. These findings suggest that µ-opioid receptors of LH can be critical to panic attack-related symptoms and facilitate the unconditioned fear-induced antinociception produced by LH neurons activation.