Sulfur dioxide derivatives produce antidepressant- and anxiolytic-like effects in mice

Sulfur dioxide (SO₂) can be endogenously generated from sulfur-containing amino acids in animals and humans. Increasing evidence shows that endogenous SO₂ may act as a gaseous molecule to participate in many physiological and pathological processes. However, the role of SO₂ and its derivatives in the central nervous system remains poorly understood. The present study explored the protective effects of exogenous SO₂ derivatives (Na₂SO₃:NaHSO₃, 3:1 M/M) on cellular injury in vitro by using the cell proliferation assay (MTS), cell counting kit 8 assay (CCK-8), and cyto-flow assay in the corticosterone (CORT)-induced PC12 cell injury model. We also examined the antidepressant and anxiolytic effects of SO₂ derivatives on the chronic mild stress (CMS)-induced depression mouse model by using the open field test, novelty suppressed feeding test, forced swimming test, tail suspension test, and sucrose preference test. In the MTS and CCK-8 assays, we found that preexposure of SO₂ derivatives significantly blocked CORT-induced decrease of cellular survival without causing any negative effects. Results from the cyto-flow assay indicated that treatment with SO₂ derivatives could reverse CORT-induced early and late apoptosis of PC12 cells. Systemic treatment with SO₂ derivatives produced markedly antidepressant- and anxiolytic-like activities in mice under normal condition and rapidly reversed CMS-induced depressive- and anxiety-like behaviors. In conclusion, these findings indicate that exogenous SO₂ derivatives show protective properties against the detrimental effects of stress and exert antidepressant- and anxiolytic-like actions. The present study suggests that exogenous SO₂ derivatives are potential therapeutic agents for the treatment of depression, anxiety, and other stress-related diseases.