Chronic stress impairs rotarod performance in rats: implications for depressive state.

Exposure to chronic stress is thought to precipitate or exacerbate several neuropsychiatric disorders such as depression. Here, we examined the effects of chronic stress administered by water immersion and restraint (2 h/day) for 4 weeks followed by a 10-day recovery period on rotarod performance. The time course study revealed that the riding time on a rotating rod was not affected at Day 1 or Week 1 of the stress period, but was significantly decreased at Week 4 and after the 10-day recovery period. However, traction performance and locomotor activity were not changed by chronic stress. We next examined the involvement of a serotonergic mechanism in the impairment of rotarod performance. The post-stress administration of a serotonergic antidepressant, trazodone (10 mg/kg, daily for 10 days) significantly ameliorated the impairment of rotarod performance. A microdialysis study also revealed a decrease in the extracellular concentration of serotonin in the prefrontal cortex. These results indicate that chronic stress impairs the rotarod performance in a manner that is not due to muscle relaxation or motor dysfunction, and this impairment may imply a behaviorally depressive state mediated by a serotonergic mechanism. These findings provide insight into the underlying mechanisms of stress-induced neuropsychiatric disorders.