Lack of autoreceptor-mediated inhibitory control of dopamine release in striatal synaptosomes of D2 receptor-deficient mice

Mouse purified striatal synaptosomes were used to study the release of newly synthesised [H-3]-dopamine ([H-3]-DA) or of previously taken up [H-3]-DA. Quinpirole (QP, 10 mu M), a D2/D3 dopaminergic agonist, was found to reduce the release of newly synthesised [H-3]-DA with a larger amplitude when LF-aminopyridine (100 mu M) instead than veratridine(1 mu M) or potassium (25 mM) was used to evoke DA release. Among the different D2/D3 dopaminergic agonists tested R(-)-propylnorapomorphine (NPA) and quinpirole were the most potent. These compounds reduced, in a concentration-dependent manner, the 4-aminopyridine-evoked release of [H-3]-DA previously taken up by synaptosomes (50% maximal inhibition). In contrast, the D3 agonist PD-128,907 had Little effect even when used at 100 nM. The QP (100 nM)-induced response was completely antagonised by sulpiride (1 mu M). Strikingly, the NPA (100 nM) and PD-128,907 (100 nM)-evoked responses were completely suppressed in D2 receptor-deficient mice. This data strongly suggest that only D2 but not D3 receptors are involved in the autoreceptor-mediated inhibition of the evoked release of [H-3]-DA. Interestingly, while amphetamine-induced release of [H-3]-DA was not modified, a slight reduction of [H-3]-DA efflux induced by the dopamine (DA) uptake inhibitor cocaine was observed in D2 receptor-deficient mice. (C) 1998 Elsevier Science B.V.