Efeito do antagonista do receptor NOP SB-612111 e imipramina no estresse de derrota social em camundongos swiss

Abstract

Depression is one of the most prevalent mental disorders in the world. Despite the availability of pharmacological treatment, some patients are not responsive, others experience severe side effects, and the antidepressants take time to produce therapeutic effects. Thus, new antidepressants are needed. Nociceptin/orfanin FQ (N/OFQ) is an endogenous peptide that binds to an inhibitory receptor coupled to G protein, called NOP receptor. NOP receptor antagonists display antidepressant activity and are able to increase resistance to acute stress. However, there are few studies investigating the preventive effects of NOP antagonists in the development of behavioral changes induced by chronic stress, when chronically administered. The aim of this study was to investigate whether treatment with NOP receptor antagonist SB-612111 prevents the development of social defeat stress-induced behavioral changes. To this aim, male Swiss mice were subjected to 10 days of social defeat stress. It was observed that after 5 days of stress, animals showed slight behavioral changes that became significant after 10 days of social defeat, and that remained significant 7 days after stress ceased. The defeated animals displayed a longer immobility time in the tail suspension test (TST), spent lesser time in the center of the open field test (OF) and they significantly lose weight. However, no behavioral changes were detected in the social interaction test (SI). Subchronic treatment with imipramine, a classic antidepressant, was carried out to validate the experimental conditions. Imipramine prevented the onset of depressive behavior in TST, but it did not protect against weight loss caused by social defeat. In addition, imipramine induced anxiogenic-like effects in the control group, while no effects were observed in the defeated mice in the OF. The repeated treatment with SB-612111, started concomitantly with social defeat stress, reduced immobility time in defeated animals 24 h and 7 days after the end of the stress, having no effects on the control group. In addition, due to the reduced sample size, other behavioral changes were not detected, thus impacting the investigation of the protective effects of this compound. In conclusion, SB612111, administered concomitantly with stress, showed lasting antidepressantlike activity in defeated animals, since the effects were observed 7 days after the end of the treatment. Neurochemical studies are necessary to support the potential increase in resistance to stress induced by blocking the NOP receptor under chronic stress conditions.