Dopamine D2 receptors were inactivated by N-ethoxycarbonyl-2-ethoxy-1,2,-dihydroxy-quinoline (
EEDQ) (6 mg/kg i.p.). The reduction in
dopamine receptors was monitored by quantitative receptor autoradiography using [125I]iodosulpiride or [3H]
raclopride as radioligands. Pretreatment of male rats with
haloperidol (0.3-3 mumol/kg i.p.) produced a dose-related, complete protection against the decrease in [125I]iodosulpiride binding induced by
EEDQ in the dorsal and ventral striata and in all cortical areas examined.
Raclopride (0.25-10 mumol/kg i.p.) produced the same pattern of effect as
haloperidol but had a weaker effect. In contrast,
remoxipride (1-40 mumol/kg i.p. or s.c.) only produced a partial protection against the
dopamine D2 receptor inactivation by
EEDQ. The results in the
EEDQ test were related to the potency to block
d-amphetamine-induced hyperlocomotion and the ability to induce bar-test
catalepsy in the rat. The potencies in the behavioural tests were found to correspond to the in vivo occupancy for
dopamine D2 receptors as evaluated by the
EEDQ-induced decrease in D2 binding. However,
remoxipride differed from both
haloperidol and
raclopride by showing a much reduced occupancy of
dopamine D2 receptors at doses with behaviourally equipotent effects. The results support earlier suggestions that
remoxipride in vivo may act on a subpopulation of
dopamine D2 receptors.