Research in affective disorders is often performed without considering sex differences, although women are predominantly affected. Consequently, the potential sex-dependent action of antidepressants remains elusive. We investigated whether Flinders sensitive line (FSL) of rats, a model of depression, would present sex-differentiated responses to antidepressant treatment. FSL and Sprague-Dawley rats were treated with clomipramine 10 mg/kg/day for 14 days. Subsequently, they were subjected to either a single session of the forced swim test or an estimation of serotonergic function in the prefrontal cortex, hippocampus, amygdala and hypothalamus. Male FSL displayed increased immobility duration, decreased active behaviours, increased serotonin tissue levels and a reduced serotonin turnover rate in most brain areas studied. Female FSL showed a distinct profile, consisting of decreased immobility latency, increased climbing duration, limited serotonergic deviations and no difference in the serotonin turnover rate in comparison with controls. Interestingly, despite baseline differences, clomipramine treatment reversed all relevant behavioural responses and increased the serotonin turnover rate in both sexes. However, the latter effect was remarkably more pronounced in females. It is concluded that, in this animal model of depression, chronic clomipramine treatment attenuated baseline sex differences in the phenotype while maintaining or intensifying the sex differentiation in the serotonergic endophenotype.

Growing evidence suggests the involvement of glutamate in mood disorders and in the response to antidepressants. However, there is no information regarding a hypothesized sex-dependent glutamatergic modulation following treatment in animal models of depression. We comparatively assayed in male and female Flinders and control Sprague-Dawley rats glutamate and aspartate tissue levels in the prefrontal cortex, hippocampus and nucleus accumbens following 14-day treatment with either 10mg/kg clomipramine or mirtazapine, intraperitoneally. Clomipramine increased cortical glutamate in both sexes and hippocampal glutamate only in female Flinders rodents. Mirtazapine had no effect on cortical glutamate content but increased hippocampal glutamate in both Flinders sexes. Neither mirtazapine nor clomipramine altered glutamate levels in the nucleus accumbens. There were no any significant differences in aspartate levels. However, in control male SD rats clomipramine and mirtazapine significantly decreased cortical aspartate levels. Our results indicate that two different types of established antidepressants induce a brain region-specific effect on glutamate content. This effect is also characterized by sex-dependent differences mainly in the hippocampus, highlighting a differentiated response of glutamate to distinct antidepressants.

Extant pharmacological options for motor conversion disorder include mainly antidepressants and benzodiazepines. We report on the case of a 42-year-old female patient with frequent daily episodes of almost complete paralysis for the last 6 months resistant to an escitalopram-lorazepam combination at adequate doses. By contrast, the adjunctive administration of low-dose amisulpride at 200 mg/d to the patient's regimen resulted in her substantial and durable improvement. We hypothesize that low-dose amisulpride, acting as a selective antagonist of D2 and D3 dopamine autoreceptors, might reverse the decreased activity of frontal and subcortical dopaminergic circuits presumably involved in motor control during hysterical paralysis.