Article
The effects of high frequency stimulation of the subthalamic nucleus on mood: a role for the lateral habenula?
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Authors
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S.K.H. Tan
- Neurochirurgische Klinik, Universitätsklinikum der RWTH Aachen, Aachen, Germany; Department of Neuroscience, Maastricht University, Maastricht, The Netherlands
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V.V. Visser-Vandewalle
- Department of Neurosurgery, Maastricht University Medical Centre, The Netherlands
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T. Sharp
- Department of Pharmacology, University of Oxford, Oxford, United Kingdom
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H. Clusmann
- Neurochirurgische Klinik, Universitätsklinikum der RWTH Aachen, Aachen, Germany
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H.W.M. Steinbusch
- Department of Neuroscience, Maastricht University, Maastricht, The Netherlands
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Y. Temel
- Department of Neuroscience, Maastricht University, Maastricht, The Netherlands; Department of Neurosurgery, Maastricht University Medical Centre, The Netherlands
| Published: | June 4, 2012 |
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Outline
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Objective: High frequency stimulation (HFS) of the subthalamic nucleus (STN) improves motor disability in Parkinson's disease. Despite sustained motor improvement, a substantial number of patients develop post-operative behavioural complications, including depression. Our previous studies demonstrated that STN HFS inhibits serotonin (5-HT) neurotransmission. This is possibly responsible for the behavioural side effects. Interestingly, a direct projection from the STN to the 5-HT system does not exist. We hypothesize that the lateral habenula (LH) is an important structure in STN HFS induced behavioural side effects and inhibition of 5-HT neurotransmission. In this study, we investigated the role of the LH in STN HFS-induced changes in mood.
Methods: Naïve male Sprague-Dawley rats (n = 40) were implanted with bilateral STN stimulation electrodes (STN HFS or sham HFS) and treated with bilateral LH injections (quinolinic acid lesions or vehicle injections). The rats were divided in the following groups: 1) Sham HFS + LH vehicle injected controls (n = 10); 2) STN HFS + LH vehicle injections (n = 10); 3) Sham HFS + LH quinolinic acid lesions (n = 10) and 4) STN HFS + LH quinolinic acid lesions (n = 10). Stimulation was performed with clinically relevant parameters (130 Hz, 60 us, 100 uA). Sham HFS animals received STN electrode implantations but were not stimulated. Motor, anxiety and mood related behaviour was assessed.
Results: STN HFS and LH lesions did not alter spontaneous locomotor activity in the open field test in naïve rats. The times spent in the open/closed arms of the elevated zero maze was not altered by STN HFS or LH lesions, reflecting unchanged anxiety-like behaviour. STN HFS resulted in decreased sucrose consumption in the sucrose intake test and decreased food consumption in the food intake test reflecting anhedonic-like behaviour. Interestingly, LH lesions prevented STN HFS induced decrease of sucrose intake but not food intake.
Conclusions: Our experiments demonstrate STN HFS to induce changes in mood related behaviour, but not in motor and anxiety behaviour. This might be mediated through STN HFS-induced inhibition of 5-HT neurotransmission. The LH may be a key structure between the STN and dorsal raphe 5-HT system important in the regulation of mood.
