A comparison of the effects of the dopamine partial agonists aripiprazole and (−)-3-PPP with quinpirole on stimulated dopamine release in the rat striatum: Studies using fast cyclic voltammetry in vitro

The effects of aripiprazole, (-)-(3-hydroxyphenyl)-N-n-propylpiperidine
((-)-3-PPP) and quinpirole on single and multiple pulse stimulated dopamine
release were investigated using the technique of fast cyclic voltammetry (FCV) in
isolated rat striatal slices. Aripiprazole and (-)-3-PPP had no
significant effect on single pulse dopamine release at concentrations from 10nM
to 10mM indicating low agonist activity. The compounds failed to
potentiate 5 pulse stimulated release of dopamine although inhibitory effects
were seen at 10 mM for aripiprazole. Both compounds were
tested against the concentration-response curve for quinpirole¿s inhibition of
stimulated single pulse dopamine release. Aripiprazole and (-)-3-PPP shifted
the concentration-response curve for quinpirole to the right. In each case this
was a greater than a 100-fold shift for the 10 mM test compound. Whilst
these results indicate that both compounds show little agonist activity on
dopamine release and significant antagonism of the inhibitory effect of
quinpirole on dopamine release, whether they are functionally selective dopamine
D2 ligands remains controversial.