title: Control of the subthalamic innervation of substantia nigra pars reticulata by D1 and D2 dopamine receptors.
abstract: 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 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 D1-class receptor agonist, increased evoked EPSCs by approximately 30% whereas the D2-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 approximately 25%. These apparently opposing actions were blocked by the specific D1- and D2-class receptor antagonists: R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetra-hydro-1H-3-benzazepinehydrochloride (SCH 23390) and S-(-)-5-amino-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.
authors.affiliation: Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y Estudios Avanzados, Universidad Nacional Autónoma de México, Mexico City, DF 04510 México.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Ibañez-Sandoval
authors.forename: Adán
authors.initials: A
authors.lastname: Hernández
authors.forename: Benjamin
authors.initials: B
authors.lastname: Florán
authors.forename: Elvira
authors.initials: E
authors.lastname: Galarraga
authors.forename: Dagoberto
authors.initials: D
authors.lastname: Tapia
authors.forename: Rene
authors.initials: R
authors.lastname: Valdiosera
authors.forename: David
authors.initials: D
authors.lastname: Erlij
authors.forename: Jorge
authors.initials: J
authors.lastname: Aceves
authors.forename: José
authors.initials: J
authors.lastname: Bargas
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D009433:Neural Inhibition / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013378:Substantia Nigra / Q000502:physiology*; D020531:Subthalamic Nucleus / Q000502:physiology*
chemical_list: D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2