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1Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y Estudios Avanzados; 2Departamento de Biofísica, Instituto de Fisiología Celular; and 3Neurociencias, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México, Federal District, Mexico City, Mexico
Submitted 26 June 2006; accepted in final form 3 August 2006
The effects of activating dopaminergic D2/3 and D4 receptors during activation of the subthalamic projection to the globus pallidus (GP) were explored in rat brain slices using the whole cell patch-clamp technique. Byocitin labeling and both orthodromic and antidromic activation demonstrated the integrity of some subthalamopallidal connections in in vitro parasagittal brain slices. Excitatory postsynaptic currents (EPSCs) that could be blocked by CNQX and AP5 were evoked onto pallidal neurons by local field stimulation of the subthalamopallidal pathway in the presence of bicuculline. Bath application of dopamine and quinpirole, a dopaminergic D2-class receptor agonist, reduced evoked EPSCs by about 35%. This effect was only partially blocked by sulpiride, a D2/3 receptor antagonist. The sulpiride-sensitive reduction of the subthalamopallidal EPSC was associated with an increase in the paired-pulse ratio (PPR) and a reduction in the frequency but not the mean amplitude of spontaneous EPSCs (sEPSCs), indicative of a presynaptic site of action, which was confirmed by variancemean analysis. The sulpiride-resistant EPSC reduction was mimicked by PD 168,077 and blocked by L-745,870, selective D4 receptor agonist and antagonist, respectively, suggesting the involvement of D4 receptors. The reduction of EPSCs produced by PD 168,077 was not accompanied by changes in PPR or the frequency of sEPSCs; however, it was accompanied by a reduction in mean sEPSC amplitude, indicative of a postsynaptic site of action. These results show that dopamine modulates subthalamopallidal excitation by presynaptic D2/3 and postsynaptic D4 receptors. The importance of this modulation is discussed.
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