Modulation of Extracellular Levels of 5-HT in the Caudate Putamen of Freely Moving Rats by High Frequency Stimulation of the Subthalamic Nucleus

Electrical high frequency stimulation (HFS) in the subthalamic nucleus (STN) has been shown to have a therapeutic effect in several movement disorders. But, debilitating psychiatric effects like depression and suicidality are occasionally seen and might be caused by the changes in the serotoninergic activity. Previous studies could show that HFS of the STN results in inhibition of the serotonergic neurons originating in the dorsal raphe nucleus. The aim of this study was to characterize the effect of HFS (124 Hz, 0.5 mA) in the STN, on the extracellular levels of serotonin, dopamine and their metabolites HIAA, DOPAC and HVA in the caudate-putamen (CPu) in conscious and freely moving rats. Extracellular levels of the neurotransmitters and their metabolites were quantified using high performance liquid chromatography with electrochemical detection. Under HFS conditions, a significant reduction in the extracellular levels of serotonin was observed. Cessation of HFS showed a recovery back to basal levels. Dopamine levels were not affected, although significant increase of its metabolites DOPAC and HVA were measured. In the case of low frequency stimulation (LFS), levels of serotonin and its metabolite HIAA remained unchanged, while the levels of dopamine metabolites, DOPAC and HVA, showed a significant decline. These results demonstrate evidence for a strong linkage between HFS in the STN and reduction of the levels of serotonin in the caudate-putamen, which is likely responsible for psychiatric side effects seen in Parkinsonian patients who are treated with STN stimulation.