GABAB receptors modulate depolarization-stimulated [3H]glutamate release in slices of the pars reticulata of the rat substantia nigra

GABAB 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 GABAB receptors decrease the glutamate release from these terminals, we have explored if the effect of GABAB receptors also opposed the effect of the dopamine D1 receptors. The effect of baclofen, a selective GABAB-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 GABAB 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 GABAB receptors restrain the excitatory input from the subthalamic nucleus and stimulate motor behavior.