Fabrício Calvo1,2,3,4, Rafael Carvalho Almada1,4,5, Tayllon Dos Anjos-Garcia1,4,6, Luiz Luciano Falconi-Sobrinho1,4,5,6, Tatiana Paschoalin-Maurin1,4,5, Guilherme Bazaglia-de-Sousa1,4,5,6, Priscila Medeiros1,4,5, Juliana Almeida da Silva1,4,5,6, Bruno Lobão-Soares1,4,5,7, Norberto Cysne Coimbra1,4,5,6. 1. 1 Department of Pharmacology, University of São Paulo (FMRP-USP), Ribeirão Preto (SP), Brazil. 2. 2 Department of Pharmacology, São Lucas College, Porto Velho (RO), Brazil. 3. 3 Aparício Carvalho Integrative College (FIMCA), Porto Velho (RO), Brazil. 4. 4 Ophidiarium LNN-FMRP-USP/INeC, University of São Paulo (FMRP-USP), Ribeirão Preto (SP), Brasil. 5. 5 Behavioural Neurosciences Institute (INeC), Ribeirão Preto (SP), Brazil. 6. 6 NAP-USP-Neurobiology of Emotions Research Centre (NuPNE), University of São Paulo (FMRP-USP), Ribeirão Preto (SP), Brazil. 7. 7 Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte (UFRN), Natal (RN), Brazil.
Abstract
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 µ1-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 µ1-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 µ1-opioid receptor antagonist naloxonazine into the IC at different concentrations (1.0, 3.0 and 5.0 µg/0.2 µL) 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 µ1-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 µ1-opioid receptor signalling activity within the IC modulates anxiety- and panic attack-related behaviours in dangerous environments.
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 µ1-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 µ1-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 µ1-opioid receptor antagonist naloxonazine into the IC at different concentrations (1.0, 3.0 and 5.0 µg/0.2 µL) 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 µ1-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 µ1-opioid receptor signalling activity within the IC modulates anxiety- and panic attack-related behaviours in dangerous environments.
Authors: Rafael C Almada; Luiz Luciano Falconi-Sobrinho; Juliana A da Silva; Carsten T Wotjak; Norberto C Coimbra Journal: Psychopharmacology (Berl) Date: 2022-06-02 Impact factor: 4.415
Authors: B B de Paula; E B Vieira-Rasteli; F Calvo; N C Coimbra; C R A Leite-Panissi Journal: Braz J Med Biol Res Date: 2022-02-16 Impact factor: 2.590