Activation of group III metabotropic glutamate receptors inhibits basal and amphetamine-stimulated dopamine release in rat dorsal striatum: an in vivo microdialysis study

Group III metabotropic glutamate (mGlu) receptors are negatively coupled to adenylate cyclase and are distributed pre-synaptically in the striatum. A behavioral study previously conducted in this laboratory shows that activat ion of this group of mGlu receptors attenuates acute amphetamine-stimulated motor activity. By administering a group III selective agonist or antagoni st via the dialysis probe, the present study employed in vivo microdialysis to evaluate the capacity of the group III selective agents to alter extrac ellular levels of dopamine in the dorsal striatum of normal and amphetamine -treated rats. It was found that the group LU agonist L-2-amino-4-phosphono butyrate (L-AP4) dose-dependently (1, 10 and 100 mu M) reduced basal levels of extracellular dopamine. In contrast, the group III antagonist alpha-met hyl-4-phosphonophenylglycine (MPPG) dose-dependently (10, 50 and 250 mu M) elevated the basal release of extracellular dopamine. This elevation was an tagonized by co-perfusion of L-AP4. Perfusion of 5-mu M amphetamine through the dialysis probe increased extracellular dopamine in the dorsal striatum . Co-perfusion of L-AP4 (100 mu M) significantly reduced amphetamine-stimul ated dopamine levels, whereas co-perfusion of L-AP4 (100 mu M) and MPPG (10 0 mu M) did not alter the capacity of amphetamine to elicit dopamine releas e. The data obtained from this study demonstrate the presence of a tonicall y active glutamatergic tone on group In mGlu receptors in the dorsal striat um to pre-synaptically regulate basal dopamine release in an inhibitory fas hion. Moreover, activation of L-AP4-sensitive group III mGlu receptors can suppress the phasic release of dopamine induced by a dopamine stimulant amp hetamine. (C) 2000 Elsevier Science B.V. All rights reserved.