Panicolytic-like effect of μ1-opioid receptor blockade in the inferior colliculus of prey threatened by Crotalus durissus terrificus pit vipers

Background: The endogenous opioid peptide system has been implicated in the neural modulation of fear and anxiety organised by the dorsal midbrain. Furthermore, previous results indicate a fundamental role played by inferior colliculus (IC) opioid mechanisms during the expression of defensive behaviours, but the involvement of the IC mu(1)-opioid receptor in the modulation of anxiety- and panic attack-related behaviours remains unclear. Using a prey-versus-snake confrontation paradigm, we sought to investigate the effects of mu(1)-opioid receptor blockade in the IC on the defensive behaviour displayed by rats in a dangerous situation. Methods: Specific pathogen-free Wistar rats were treated with microinjection of the selective mu(1)-opioid receptor antagonist naloxonazine into the IC at different concentrations (1.0, 3.0 and 5.0 mu g/0.2 mu L) and then confronted with rattlesnakes (Crotalus durissus terrificus). The defensive behavioural repertoire, such as defensive attention, flat back approach (FBA), startle, defensive immobility, escape or active avoidance, displayed by rats either during the confrontations with wild snakes or during re-exposure to the experimental context without the predator was analysed. Results: The blockade of mu(1)-opioid receptors in the IC decreased the expression of both anxiety-related behaviours (defensive attention, FBA) and panic attack-related responses (startle, defensive immobility and escape) during the confrontation with rattlesnakes. A significant decrease in defensive attention was also recorded during re-exposure of the prey to the experimental apparatus context without the predator. Conclusion: Taken together, these results suggest that a decrease in mu(1-)opioid receptor signalling activity within the IC modulates anxiety- and panic attack-related behaviours in dangerous environments.