Deep brain stimulation of the subthalamic nucleus in the 6-hydroxydopamine rat model of Parkinson's disease: Effects on sensorimotor gating

摘要

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 deficient prepulse inhibition (PPI) induced by the dopamine (DA) receptor agonist apomorphine, which is an operative measure for disturbed sensorimotor gating seen in certain neuropsychiatric disturbances.Male Sprague Dawley rats with bilateral lesions of the nigrostriatal DA system (striatal injection of 6-OHDA or vehicle for sham-lesion) were bilaterally implanted with electrodes for DBS into the STN. After determination of individual thresholds rats were stimulated (130. Hz, 80μs pulse width) or sham-stimulated for epochs of six days. On the sixth day of each epoch rats were tested for PPI of the acoustic startle response after apomorphine or vehicle injection in a within randomized cross-over design.Stimulation of the STN improved PPI in vehicle-treated (control) rats, but deteriorated PPI after apomorphine treatment. This effect was more pronounced in sham-lesioned rats. Furthermore, in lesioned rats the startle reaction was marginally enhanced without effect of stimulation or apomorphine treatment.These data suggest that STN DBS interacts with dopaminergic action. With respect to functional neurosurgery, STN DBS alone may improve certain aspects of psychiatric disturbances, but may have a different impact when combined with dopaminergic medication.