Selective serotonin reuptake inhibitors fluvoxamine and paroxetine restore forced exercise-induced temperature dysregulation in ovariectomized mice

Hot flushes are one of the most frequent symptoms in menopausal women. Selective serotonin reuptake inhibitors (SSRIs) are considered to be first-line therapy for the treatment of hot flushes in women for whom hormone therapy is contraindicated. Recently, we have proposed forced exercise-induced flushing of tail skin in ovariectomized mice as a new experimental model of temperature dysregulation in menopausal hot flushes. In the present study, to validate this animal model as a tool for testing potential compounds for the treatment of menopausal hot flushes, we examined the effects of two SSRIs (fluvoxamine and paroxetine) on forced exercise-induced flushing of tail skin in ovariectomized mice, and compared it with that of estradiol replacement (1 mg/kg/week for 3 weeks, i.m.). Treatment with fluvoxamine (20 mg/kg, i.p.) or paroxetine (10 mg/kg, i.p.) completely inhibited forced exercise-induced flushing of tail skin in ovariectomized mice, and the effect of each was comparable to that of estradiol replacement. It is believed that the present findings provide the first experimental evidence to support the anti-flushing effects of SSRIs, such as fluvoxamine and paroxetine, in a clinical setting. An animal model with forced exercise probably serves as a useful experimental tool for evaluating the effects of different agents on hot flushes.