The group I metabotropic glutamate receptor antagonist S-4-CPG modulates the locomotor response produced by the activation of D1-like, but not D2-like, dopamine receptors in the rat nucleus accumbens.

Functional interactions between dopamine (DA) and glutamate neurotransmissions in both the dorsal and the ventral striatum have been described for long time. However, there is much controversy as to whether glutamate transmission stimulates or attenuates DA release and locomotor activity. We investigated the functional interactions on locomotor activity between group I metabotropic glutamatergic receptors (mGlu receptors) and both D1-like and D2-like DA receptors in the rat nucleus accumbens. Intra-accumbens administration of the selective group I mGlu receptor antagonist S-4-CPG (0.2 or 2 microg per side), which had no effect when injected alone, prevented the increase in locomotor activity produced by the selective D1-like receptor agonist SKF 38393 (1 microg per side). Co-administration with S-4-CPG of the group I mGlu receptor agonist DHPG, but not of the group II mGlu receptor agonist APDC or the group III mGlu receptor agonist AP4, reversed the antagonistic effect of S-4-CPG on the SKF 38393-induced increase in locomotor activity. This indicates that the antagonistic effect of S-4-CPG could result from an action at the group I mGlu receptors. In contrast, administration of S-4-CPG showed no effect on the locomotor responses produced by either the selective D2-like receptor agonist LY 171555 (1 microg per side) or a mixed solution of SKF 38393 + LY 171555 (1 microg per side each). Altogether, these results confirm that glutamate transmission may control locomotor function through mGlu receptors in a DA-dependent manner, and further indicate that group I mGlu receptors would interact with D1-like receptors, but not D2-like receptors, to modulate DA transmission and locomotor activity.