Microinjection of valproic acid into the ventrolateral orbital cortex exerts an antidepressant-like effect in the rat forced swim test.

Valproic acid (VPA), widely used as mood stablizer, has been shown therapeutic effects in controlling both episodes of mania and depression. The neurobiological actions by which valproic acid exerts these effects have not been established. Ventrolateral orbital cortex (VLO) is a subregion of orbitofrontal cortex (OFC) that has been closely associated with depression. However, there are few studies aimed at investigating the role of the VLO in the neurobiology of depression. In the present study, we investigated the effects on rat forced swimming test (FST) of microinjected VPA into the VLO. A single bilateral infusion of VPA into the VLO and repeated systemic administration of fluoxetine, a chemical antidepressant, significantly decreased the immobility time in the FST as compared to saline-treated controls. The effects observed in the FST paradigms could not be attributed to non-specific increases in activity since microinjection of VPA into the VLO or fluoxetine treatment did not cause general increases in locomotion test. The results provide first support for the involvement of VLO in regulating depressive-like behavior and indentify potentially important characteristics of VPA in contributing to the therapeutic action of antidepressant treatment.