Inhibition of 5-HT neuron activity and induction of depressive-like behavior by high-frequency stimulation of the subthalamic nucleus

• DOI: 10.1073/pnas.0704144104
• Publication Date: 2007-10-18T01:25:13Z
• Authors: Yasin Temel; Laura J. Boothman; Arjan Blokland; Peter J. Magill; Harry W. M. Stein...; Veerle Visser-Van...; Trevor Sharp
• Keywords: Subthalamic Nucleus; Dorsal raphe nucleus; Premovement neuronal activity; Depression

Bilateral, high-frequency stimulation (HFS) of the subthalamic nucleus (STN) is surgical therapy choice for movement disability in advanced Parkinson's disease (PD), but this procedure evokes debilitating psychiatric effects, including depressed mood, unknown neural origin. Here, we report unexpected finding that HFS STN inhibits midbrain 5-hydroxytryptamine (5-HT) neurons to evoke depression-related behavioral changes. We found bilateral consistently inhibited (40-50%) firing rate 5-HT dorsal raphe rat, not neighboring non-5-HT neurons. This effect was apparent at clinically relevant parameters (> or =100 Hz, > =30 microA), elicited by either remote structures STN, and still present rat models PD. also evoked clear-cut, depressive-like behavior a widely used experimental paradigm depression (forced swim test), observed PD model. Importantly, reversed selective 5-HT-enhancing antidepressant, thereby linking change decreased neuronal activity. Overall, these findings link reduced function effects patients provide rational basis their clinical management. More generally, powerful interaction between system uncovered here offers insights into high level comorbidity basal ganglia mood disorder.