Neuromodulatory actions of dopamine on synaptically-evoked neostriatal responses in slices

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Abstract
The present experiments were designed to further examine the hypothesis that receptor subtype determines the direction of dopamine's (DA) ability to modulate neostriatal neuronal responses. We have reported that DA potntiates responses medited by activation of N‐methyl‐d‐aspartate (NMDA) receptors, but attenuates responses mediated by activation of non‐NMDA rceptors in neocortex [Cepeda et al. (1992b) Synapse, 11:330]. and neostriatum [Cepeda et al. (1993) Proc. Natl. Acad. Sci. U.S.A., 90:9576–9580]. In thse studies, rsponses to excitatory amined whetere this differential modulpation also applies to components of synaptic responses evoked by electrical Stimulation of Neostriatal afferents and mediated by activation of specific subtypes of EAA receptors. Using brain slices, the actions of DA and its receptor specific agonistss on components of neostriatal synaptic responses that were mediated either by NMDA or non‐NMDA rceptors were assessed. Responses mediatd by NMDA recepotors were potentiated by DA while those mediated by non‐NMDA receptors were attenuated. These findings provide further support for the htpothesis that the direction of modulatory action of DA is determindd bt the spcific subtype of EAA rdeptor activted. In addition, the enhancement of NMDA rceptor‐mediated responses was mimicked bty application of SKF 38393, D1 receptor agonist. Quinpirole, a D2 redceptor agonist, consistently attenuated responses mediated by activation of non‐NMDA receptors. Thus, the complex modultory actions of DA are dependent upon combinations of co‐activation kof specific subtypes of EAA and DA receptors. These findings are of clijnical relecance since the actions of DA and EAAs khave been implicated in neurological and affective disorder.