Regulation of striatal dopamine release by metabotropic glutamate receptors

In vivo microdialysis in conscious rats was used to assess the effect of metabotropic glutamate receptor stimulation on striatal dopamine release. Local application of the metabotropic glutamate agonist (+/-)-trans-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), via a microdialysis probe, produced a concentration-dependent response: infusion of 50 microM ACPD did not produce a significant effect on extracellular dopamine levels, while application of 100 microM or 500 microM ACPD increased dopamine release by approximately 50% or 100%, respectively. To examine the contribution of impulse flow and multisynaptic mechanisms to the ACPD-induced increase in dopamine release, 500 microM ACPD were coapplied with 2 microM tetrodotoxin (TTX). An increase in extracellular dopamine levels was observed after the application of 500 microM ACPD, despite the presence of TTX. To further study the actions of metabotropic glutamate receptor-stimulation on terminal release characteristics of dopamine, the effect of ACPD on 40 mM K+-stimulated dopamine release was investigated. It was found that application ofACPD reduces dopamine release in response to K+ stimulation. These data suggest that during basal conditions, metabotropic glutamate receptor activation facilitates striatal dopamine release, possibly through presynaptic, impulse-independent mechanisms. However, during conditions of hyperstimulation, activation of metabotropic receptors, in contrast to ionotropic receptors, reduces excess dopamine release.