Bloqueio do receptor NOP modula comportamento relacionado a ansiedade em camundongos expostos a estresse inescapável

Abstract

Depression and anxiety frequently co-occurs and it has important clinical implications. Previous studies showed that activation of nociceptin/orphanin FQ receptor (NOP) elicits anxiolytic effects, while its blockade promotes consistent antidepressant actions. NOP antagonists are effective in reversing footshocksinduced depressive-like behaviors, but their effects on stress-induced anxiety are still nuclear.This study aimed to investigate the effects of the NOP antagonist SB-612111 on footshock stress-induced anxiety behaviors. Male Swiss mice were exposed to inescapable electric footshock stress, and behavioral phenotype was screened based on the ability to escape from footshock (ie., helpless or non helpless). Animals were then treated with diazepam (1 mg/kg) and SB-612111 (0.1-10 mg/kg) and their behavior was assessed in the elevated plus-maze (EPM) and open field test. When compared to non stressed mice, helpless, but not non helpless, animals displayed significant reduction in the time spent in and entries into open arms in the EPM. Diazepam significantly increased open arms exploration in helpless, non helpless, and non stressed mice. However, the treatment with the NOP antagonist SB-612111 was inactive in naïve mice, while it reversed anxiogenic-related behaviors in helpless, and increased anxiety states in non helpless animals. No effects on locomotion were observed. Helpless mice displayed increased anxiety compared to non stressed and non helpless animals, thus it can be used as animal model to investigate anxiety/depression co-morbidity. Additionally, SB-612111 modulated anxiety-like behaviors in animals depending on individual stress susceptibility. Ultimately, NOP antagonists can be useful for treating anxiety in depressive patients.