Group II metabotropic glutamate receptor-mediated regulation of dopamine release from slices of rat nucleus accumbens

The role of metabotropic glutamate receptors (mGluRs) in the regulation of dopamine release in the rat nucleus accumbens was investigated. Fifteen millimolar of KCl stimulated the release of [3H]dopamine from the slices of the rat nucleus accumbens. Both an mGluR agonist 1S,3R-1-amino-cyclopentane-1,3-dicarboxylate (ACPD) and a preferential group II mGluR agonist, (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (L-CCG-1), significantly inhibited the KCl-evoked [3H]dopamine release in the nucleus accumbens. This inhibitory effect of L-CCG-1 on the KCl-evoked dopamine release was significantly attenuated by preferential group II mGluR antagonists such as (2S,3S,4S)-2-methyl-2-(carboxypropyl)glycine (MCCG) and (RS)-α-methyl-4-tetrazolylphenylglycine (MTPG); in contrast, the preferential group III mGluR agonist L-2-amino-4-phosphonobutylate (L-AP4), failed to show any effect on the KCl-evoked [3H]dopamine release in the nucleus accumbens. Moreover, the inhibitory effect of L-CCG-1 on the KCl-evoked [3H]dopamine release from the slices of the rat nucleus accumbens was preserved in the presence of tetrodotoxin. These results show that group II mGluRs may play a more significant role in regulating dopamine release than group III mGluRs, and that the group II mGluRs may negatively regulate dopamine release, presumably through those expressed at the dopaminergic nerve terminals or through those expressed at glutamatergic nerve terminals in the nucleus accumbens.