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Bargas, J; Galarraga, E; Ibanez-Sandoval, O; Hernandez, A; Floran, B; Tapia, D; Valdiosera, R; Erlij, D; Aceves, J (2006)

CONTROL OF THE SUBTHALAMIC INNERVATION OF SUBSTANTIA NIGRA PARS RETICULATA BY D-1 AND D-2 DOPAMINE RECEPTORS

J NEUROPHYSIOL 95(3):1800-1811
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The effects of activating dopaminergic D-1 and D-2 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 6-cyano-7-nitroquinoxalene-2,3-dione and D-(-)-2-amino-5-phosphonopentanoic acid were evoked onto reticulata GABAergic projection neurons by local field stimulation inside the subthalamic nucleus in the presence of bicuculline. Bath application of (RS)- 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3- benzazepine hydrochloride (SKF-38393), a dopaminergic D-1-class receptor agonist, increased evoked EPSCs by similar to 30% whereas the D-2-class receptor agonist, trans-(-)- 4aR- 4,4a, 5,6,7,8,8a, 9-octahydro-5-propyl-1H- pyrazolo( 3,4-g) quinoline (quinpirole), reduced EPSCs by similar to 25%. These apparently opposing actions were blocked by the specific D-1- and D-2-class receptor antagonists: R-(+)-7-chloro-8-hydroxy- 3-methyl-1-phenyl-2,3,4,5-tetra-hydro-1H-3-benzazepine hydrochloride (SCH 23390) and S-(-)-5-anino- sulfonyl-N-[(1-ethyl-2- pyrrolidinyl)- methyl]-2-methoxybenzamide ( 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 on 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.