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 re lease. Local application of the metabotropic glutamate agonist (+/-)-t rans-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), via a microdial ysis probe, produced a concentration-dependent response: infusion of 5 0 mu M ACPD did not produce a significant effect on extracellular dopa mine levels, while application of 100 mu M or 500 mu M ACPD increased dopamine release by approximately 50% or 100%, respectively. To examin e the contribution of impulse flow and multisynaptic mechanisms to the ACPD-induced increase in dopamine release, 500 mu M ACPD were coappli ed with 2 mu M tetrodotoxin (TTX). An increase in extracellular dopami ne levels was observed after the application of 500 mu M ACPD, despite the presence of TTX. To further study the actions of metabotropic glu tamate receptor-stimulation on terminal release characteristics of dop amine, the effect of ACPD on 40 mM K+-stimulated dopamine release was investigated. It was found that application of ACPD reduces dopamine r elease in response to K+ stimulation. These data suggest that during b asal conditions, metabotropic glutamate receptor activation facilitate s striatal dopamine release, possibly through presynaptic, impulse-ind ependent mechanisms. However, during conditions of hyperstimulation, a ctivation of metabotropic receptors, in contrast to ionotropic recepto rs, reduces excess dopamine release. (C) 1998 Wiley-Liss, Inc.