M. Lhirondel et al., LACK OF AUTORECEPTOR-MEDIATED INHIBITORY CONTROL OF DOPAMINE RELEASE IN STRIATAL SYNAPTOSOMES OF D2 RECEPTOR-DEFICIENT MICE, Brain research, 792(2), 1998, pp. 253-262
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 larg
er 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, i
n a concentration-dependent manner, the 4-aminopyridine-evoked release
of [H-3]-DA previously taken up by synaptosomes (50% maximal inhibiti
on). In contrast, the D3 agonist PD-128,907 had Little effect even whe
n used at 100 nM. The QP (100 nM)-induced response was completely anta
gonised by sulpiride (1 mu M). Strikingly, the NPA (100 nM) and PD-128
,907 (100 nM)-evoked responses were completely suppressed in D2 recept
or-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 r
elease of [H-3]-DA was not modified, a slight reduction of [H-3]-DA ef
flux induced by the dopamine (DA) uptake inhibitor cocaine was observe
d in D2 receptor-deficient mice. (C) 1998 Elsevier Science B.V.