title: GABA(B) receptors modulate depolarization-stimulated [³H]glutamate release in slices of the pars reticulata of the rat substantia nigra.
abstract: GABA(B) receptors decrease the release of GABA from the striatal terminals within the pars reticulata of the substantia nigra by opposing the increase in the release caused by dopamine D₁ receptors. The dopamine D₁ receptors also increase the release of glutamate from subthalamic terminals in the pars reticulata. Because GABA(B) receptors decrease the glutamate release from these terminals, we have explored if the effect of GABA(B) receptors also opposed the effect of the dopamine D₁ receptors. The effect of baclofen, a selective GABA(B)-receptor agonist, was tested on the release of [³H]glutamate caused by highly (40 mM) concentrated K(+) solutions in slices of the pars reticulata. Baclofen decreased (the concentration causing 50% inhibition, IC₅₀, was 8.15 μM) the increase in the release of the [³H]glutamate caused by the dopamine D₁ receptors and it also decreased (IC₅₀ was 0.51 μM) this release in the absence of the activation of the dopamine D₁ receptors. The GABA(B) receptors appear then to inhibit glutamate release in two ways; one dependent on the activation of the dopamine D₁ receptors and the other independent of such activation. The protein kinase A-inhibitor H89 blocked the increase in the release of the [³H]glutamate caused by the dopamine D₁ receptors, though it did not block the dopamine D₁ receptor-independent baclofen inhibition of the release. This finding indicates that this inhibition was not via the protein kinase A signal-transduction pathway. N-ethylmaleimide, an alkylating agent that inactivates pertussis toxin-sensitive Gi proteins, eliminated both the dopamine D₁ receptor-dependent and -independent baclofen inhibition, showing that both were mediated by these proteins. The injection of baclofen into the pars reticulata of unanesthetized rats caused contralateral rotation, suggesting a reduced glutamate release from the subthalamic terminals, thereby stopping the inhibition of the premotor thalamic nuclei, causing locomotion. Our data suggest that GABA(B) receptors restrain the excitatory input from the subthalamic nucleus and stimulate motor behavior.
authors.affiliation: Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnio Nacional, Apartado 14-740, México D.F., México.
authors.forename: Hernán
authors.initials: H
authors.lastname: Cortés
authors.forename: Francisco
authors.initials: F
authors.lastname: Paz
authors.forename: David
authors.initials: D
authors.lastname: Erlij
authors.forename: Jorge
authors.initials: J
authors.lastname: Aceves
authors.forename: Benjamín
authors.initials: B
authors.lastname: Florán
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D018491:Dopamine Agonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009928:Organ Specificity; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism; D018080:Receptors, GABA-B / Q000502:physiology*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D020531:Subthalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D014316:Tritium
chemical_list: D018491:Dopamine Agonists; D058786:GABA-B Receptor Agonists; D009419:Nerve Tissue Proteins; D047428:Protein Kinase Inhibitors; D017447:Receptors, Dopamine D1; D018080:Receptors, GABA-B; D014316:Tritium; D018698:Glutamic Acid; D017868:Cyclic AMP-Dependent Protein Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go