Effects of the Dopamine D2 Selective Receptor Antagonist Remoxipride on Dopamine Turnover in the Rat Brain after Acute and Repeated Administration

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Abstract
The effects of the dopamine D2 selective receptor antagonist, remoxipride, on dopamine turnover in the rat brain were studied after acute and repeated administration and compared with the effects of haloperiodol. Acute administration of remoxipride produced a dose‐dependent increase of the concentrations of DOPAC and HVA in both striatum and olfactory tubercle+nucleus accumbens. The maximal effect of both acute remoxipride and haloperidol on dopamine turnover was attained approximately 2 hours after a single intraperitoneal administration, whereas a biphasic response was seen after oral remoxipride. Tolerance to the effects of repeated haloperidol (20 μmol/kg orally) treatment on dopamine turnover was observed as soon as after 3 days, whereas no such tolerance could be found during the first 15 days of repeated treatment with remoxipride (20 μmol/kg orally). A dose‐related tolerance to the effects of remoxipride was, however, seen at higher dosages (40, 150 and 600 μmol/kg orally) and after a longer period (6 months) of treatment.
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