Long-Term Sildenafil–Dapoxetine Administration Exerts Anxiolytic-Like Effects and Partial Antioxidant Augmentation but Does Not Mitigate Neuroinflammation in a Methyldopa-Induced Mouse Model: A Comparison with Imipramine
Abstract
Anxiety and depression are prevalent neuropsychiatric disorders associated with oxidative/nitrosative stress, neuroinflammation, and monoaminergic imbalances. Methyldopa, a centrally acting antihypertensive, reportedly induces anxiety- and depressive-like states alongside oxidative stress and inflammatory responses. Sildenafil-dapoxetine (SIL-DAP) fixed-dose combination, a phosphodiesterase-5 inhibitor plus a short-acting selective serotonin reuptake inhibitor, is prescribed for erectile dysfunction and premature ejaculation, but its central nervous system effects remain underexplored. This study evaluated the long-term neurobehavioral and biochemical effects of SIL-DAP in a methyldopa-induced mouse model. Adult male mice were divided into seven groups (n=6 per group per time point) and treated orally every two days for 30 or 60 days: vehicle (10 mL/kg distilled water), methyldopa (1 mg/kg), sildenafil (1 mg/kg), dapoxetine (1 mg/kg), SIL-DAP (2.5 and 5 mg/kg of the combination), and imipramine (1.8 mg/kg). Anxiety- and depressive-like behaviours were assessed using the elevated plus maze, light-dark transition test, tail suspension test, social interaction test, and open field test. Brain oxidative stress markers (nitrite, catalase, superoxide dismutase, myeloperoxidase) were subsequently assayed. Methyldopa elicited robust anxiety-like behaviour, social withdrawal, and reduced locomotion, accompanied by elevated brain nitrite, decreased superoxide dismutase and catalase…
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