Artikel
Deep brain stimulation of the subthalamic nucleus in the 6-hydroxydopamine rat model of Parkinson's disease: effects on sensorimotor gating and motivation
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Veröffentlicht: | 4. Juni 2012 |
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Gliederung
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Objective: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effectively used to treat motor symptoms in Parkinson's disease (PD). Recently more attention has been paid to behavioral disturbances caused by PD itself and by STN-DBS. In the 6-hydroxydopamine (6-OHDA) PD rat model, we investigated the effect of STN-DBS on motivation and deficient prepulse inhibition induced by the dopamine receptor agonist apomorphine, which is an operant measure of disturbed sensorimotor gating.
Methods: Male Sprague Dawley rats with bilateral lesions of the nigrostriatal dopamine system (striatal injection of 6-OHDA or vehicle for sham-lesion) were bilaterally implanted with electrodes for DBS into the STN. After determination of the individual threshold, which was usually between 80 and 160 μA, rats were stimulated with 20% below this threshold with 130 Hz, 80 μs pulse width or sham-stimulated for epochs of five days. After each epoch, the rats were tested for motivation to lever press for pellet reward in a Skinner box. In addition, rats were tested for prepulse inhibition (PPI) of startle after apomorphine- and vehicle injection.
Results: Rats with 6-OHDA induced lesions were marginally less motivated to lever-press for reward than sham-lesioned rats, which was not affected by STN-DBS. The apomorphine-induced PPI-deficit was further worsened by STN-stimulation in sham lesioned, but not in lesioned rats. In lesioned rats, the startle reaction was enhanced by the combination of STN-DBS and apomorphine.
Conclusions: These data suggest that STN-DBS affects the neuronal circuits responsible for certain behavioral symptoms after dopamine receptor activation. With respect to functional neurosurgery, STN-DBS may worsen deficient sensorimotor gating and it may also be involved in behavioral disturbances of PD patients after STN-DBS.