PERSISTENT INCREASE IN DOPAMINE RELEASE FOLLOWING ACTIVATION OF METABOTROPIC GLUTAMATE RECEPTORS IN THE RAT NUCLEUS-ACCUMBENS

Intracerebral microdialysis technique was utilized to study the effect of the metabotropic glutamate receptor agonist, 1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), on extracellular dopamine concentration in the nucleus accumbens of unanesthetized, freely moving rats. Perfusion of 1 mM (1S,3R)-ACPD, a selective metabotropic glutamate receptor agonist, through the microdialysis probe caused a significant and persistent increase in extracellular dopamine level in the nucleus accumbens, which disappeared 2 h after perfusion of (1S,3R)-ACPD was discontinued. On the other hand, a temporary increase in dopamine overflow was observed when 1 and 3 mM N-methyl-D-aspartate (NMDA), an ionotropic glutamate receptor agonist, was perfused into the nucleus accumbens. Application of 1 mM (1R,3S)-ACPD, an inactive isomer, into the nucleus accumbens had no effect on the extracellular dopamine concentration. The metabotropic glutamate receptor antagonist alpha-methyl-4-carboxyphenylglycine (MCPG) (5 mM) did not affect the basal dopamine level, but it attenuated the (1S,3R)-ACPD-evoked dopamine overflow in the nucleus accumbens when applied concurrently with 1 mM (1S,3R)-ACPD. These results suggest that a long-lasting dopamine overflow following activation of metabotropic glutamate receptors contrasts with a transient one in response to NMDA receptor activation in the nucleus accumbens.