The group I metabotropic glutamate receptor antagonist S-4-CPG modulates the locomotor response produced by the activation of D-1-like, but not D-2-like, dopamine receptors in the rat nucleus accumbens

Functional interactions between dopamine (DA) and glutamate neurotransmissi ons in both the dorsal and the ventral striatum have been described for lon g time. However, there is much controversy as to whether glutamate transmis sion stimulates or attenuates DA release and locomotor activity. We investi gated the functional interactions on locomotor activity between group I met abotropic glutamatergic receptors (mGlu receptors) acid both D-1-like and D -2-like DA receptors in the rat nucleus accumbens. Intra-accumbens administ ration of the selective group I mGlu receptor antagonist S-4-CPG (0.2 or 2 mug per side), which had no effect when injected alone, prevented the incre ase in locomotor activity produced by the selective D-1-like receptor agoni st SKF 38393 (1 mug 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 a n 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 sele ctive D-2-like receptor agonist LY 171555 (1 mug per side) or a mixed solut ion of SKF 38393 + LY 171555 (1 mug per side each). Altogether, these resul ts confirm that glutamate transmission may control locomotor function throu gh mGlu receptors in a DA-dependent manner, and further indicate that group I mGlu receptors would interact with D-1-like receptors, but not D-2-like receptors, to modulate DA transmission and locomotor activity.