Persistent increase in dopamine release following activation of metabotropic glutamate receptors in the rat nucleus accumbens

Abstract

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 (1 S,3 R)-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 (1 S,3 R)-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 (1 R,3 S)-ACPD, an inactive isomer, into the nucleus accumbens had no effect on the extracellular dopamine concentration. The metabotropic glutamate receptor antagonist α-methyl-4-carboxyphenylglycine (MCPG) (5 mM) did not affect the basal dopamine level, but it attenuated the (1 S,3 R)-ACPD-evoked dopamine overflow in the nucleus accumbens when applied concurrently with 1 mM (1 S,3 R)-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.