The effects of chronic treatment with
dopamine (DA) D1 and D2 receptor antagonists were evaluated in eight cebus apella monkeys with mild
oral dyskinesia after previous
haloperidol treatment.
SCH 23390 (D1 antagonist) was given daily to investigate the direct behavioural effect during long-term treatment and the subsequent supersensitivity to DA agonists.
Raclopride (D2 antagonist) was investigated for comparison. All drugs were given subcutaneously.
SCH 23390 and
raclopride induced dystonic syndromes,
catalepsy, sedation and reduced locomotor activity. The monkeys developed marked tolerance to the dystonic effect of
SCH 23390, while they showed increased sensibility to the dystonic effect of
raclopride. Baseline
oral dyskinesia (24 h after injection) remained unchanged during D1 antagonist treatment, while it increased during D2 antagonist treatment.
SCH 23390 induced supersensitivity to the
oral dyskinesia- and grooming-inducing effects of
SKF 81297 (D1 agonist) after 9 weeks, while the subsequent treatment with
raclopride induced supersensitivity to the reactivity- and stereotypy-inducing effects of
quinpirole (D2 receptor agonist) after 3 weeks. Because of the possibility of a carry-over effect (
SKF 81297-induced oral
hyperkinesia and grooming), other changes in
raclopride-induced behaviours cannot be ruled out. The development of tolerance to the dystonic effect of
SCH 23390 and the unchanged baseline
oral dyskinesia during
SCH 23390 treatment indicate an advantageous profile of side effects of DA D1 receptor blockade.