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1 Biofisica, Universidad Nacional Autonoma de Mexico, Mexico City, DF, Mexico
* To whom correspondence should be addressed. E-mail: jbargas{at}ifc.unam.mx.
The effects of activating dopaminergic D1 and D2 class receptors of the subthalamic projections that innervate the pars reticulata of the subtantia nigra (SNr) were explored in slices of the rat brain using the whole-cell patch-clamp technique. Excitatory postsynaptic currents (EPSCs) that could be blocked by CNQX and D-AP-5 were evoked onto reticulata GABAergic projection neurons by local field stimulation inside the subthalamic nucleus (STN) in the presence of bicuculline. Bath application of SKF-38393, a dopaminergic D1-class receptor agonist, increased evoked EPSCs by about 30% whereas the D2-class receptor agonist, quinpirole, reduced EPSCs by about 25%. These apparently opposing actions were blocked by the specific D1- and D2-class receptor antagonists: SCH 23390 and sulpiride, respectively. Both effects were accompanied by changes in the paired-pulse ratio; indicative of a presynaptic site of action. The presynaptic location of dopamine receptors at the subthalamonigral projections was confirmed by mean-variance analysis. The effects of both SKF-38393 and quinpirole could be observed upon terminals contacting the same postsynaptic neuron. Sulpiride and SCH 23390 enhanced and reduced the evoked EPSC, respectively, suggesting a constitutive receptor activation probably arising from endogenous dopamine. These data suggest that dopamine presynaptically modulates the subthalamic projection that targets GABAergic neurons of the SNr. Implications of this modulation for basal ganglia function are discussed.
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