Differential modulation of the D1-like- and D2-like dopamine receptor-induced locomotor responses by group II metabotropic glutamate receptors in therat nucleus accumbens

There is strong evidence for the existence of functional interactions betwe en metabotropic glutamate receptors and dopamine transmission in the nucleu s accumbens. In the present study, we investigated the interactions between group II mGlu receptors and D1-like- and D2-like receptors in the rat nucl eus accumbens. Administration of the selective group II metabotropic glutam ate receptor agonist APDC, which had no effect when injected alone, potenti ated the locomotor response produced by the selective DI-like receptor agon ist SKF 38393 but had no effect on those induced by the selective D2-like r eceptor agonist quinpirole (also known as LY 171555) - a compound believed to act only at D2-like presynaptic receptors when injected alone - or co-ad ministration of SKF 38393+quinpirole - a pharmacological condition thought to stimulate both D1-like receptors and presynaptic and postsynaptic D2-lik e receptors. In contrast, the selective group II mGlu receptor antagonist L Y 341495, which induced an increase in basal locomotor activity, showed no effect on the SKF 38393-induced locomotor response, but abolished that prod uced by quinpirole or SKF 38393+quinpirole. The present findings demonstrat e that stimulation of group II mGlu receptors has a cooperative and potenti ating action on the locomotor response induced by D1-like receptor activati on, whereas blockade of group II mGlu receptors has an antagonist action on the locomotor responses induced by activation of D2-like receptors. Althou gh these data are consistent from a pharmacological point of view, as the e ffects of the group II mGlu receptor antagonist LY 341495 were blocked by t he group II mGlu receptor agonist APDC and conversely, the subtle neurochem ical crosstalks underlying such a differential effect of group II mGlu rece ptors on D1-like- and D2-like DA receptors remain to be elucidated. (C) 200 1 Elsevier Science Ltd. All rights reserved.