Electrical stimulation of rat medial prefrontal cortex enhances forebrain serotonin output: implications for electroconvulsive therapy and transcranial magnetic stimulation in depression

Abstract

Decreased activity of the prefrontal cortex (PFC), as well as reduced serotonergic neurotransmission, is considered as a characteristic feature of major depression. The mechanism by which electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) achieve their antidepressant effects may involve changes in PFC activity. It is, however, still unclear whether these changes are accompanied by increased synaptic availability of serotonin (5-HT). In the present study, 5-HT efflux in the rat ventral hippocampus and amygdala was analyzed using in vivo microdialysis during low-current electrical stimulation of PFC and other cortical regions. Electrical stimulation of the medial PFC produced current-dependent increases in limbic 5-HT output in both urethane-anesthetized and behaving rats. No effects on 5-HT levels were seen after comparable stimulation of either the lateral parts of the PFC, the medial precentral area, the primary motor cortex or the parietal cortex. This pronounced regional specificity of the effect of medial PFC stimulation on limbic 5-HT output suggests that activation of this particular area might play a crucial role in such antidepressant treatments as ECT and TMS.