Sagarduy, A. 1 , Llorente, J. 1 , Miguelez, C. 1, 2 , Morera-Herreras, T. 1 , Aristieta, A. 1 , Ruiz-Ortega, J. A. 1, 2 & Ugedo, L. 1
1 Faculty of Medicine. University of the Basque Country, E-48940 Leioa (Bizkaia)
2 School of Pharmacy. University of the Basque Country, E-01006 Vitoria-Gasteiz (Araba)
The most effective treatment for Parkinson?s disease (PD), L-DOPA, induces dyskinesia (LID) after prolonged use. We have previously shown that in 6-hydroxydopamine lesioned rats rendered dyskinetic by prolonged L-DOPA administration, lesion of the subthalamic nucleus (STN) reduces LID and buspirone antidyskinetic effect. This study examined the effect of buspirone on STN neuron activity. Single-unit extracellular recordings were performed in vivo on STN neurons from four different groups, i.e., control, chronically treated with L-DOPA, lesioned and lesioned chronically treated with L-DOPA (dyskinetic) rats and in vitro cell-attached recordings. In control rats buspirone administration decreased the firing rate in a dose-dependent manner. This effect was absent in 6-OHDA lesioned rats and was not modified by acute or prolonged L-DOPA administration. In addition, in control rats the 5HT1A antagonist WAY-100635 and the D3 antagonist PD128907 prevented the effect of buspirone. Conversely, in parasagittal slices containing the STN, buspirone induced excitatory, inhibitory and also biphasic responses being only the inhibitory effect prevented by WAY-100635. Buspirone in vivo reduces the firing rate of the STN neurons through 5HT1A and D3 receptors whereas in vitro buspirone seams to show a more variable effect. Moreover, buspirone lack of effect in 6-OHDA lesioned rats, suggests that the STN may not be directly involved in its antidyskinetic effect.