Eight Cebus apella monkeys previously treated with
dopamine D1 and D2 receptor antagonists were used to elucidate the pathophysiology of acute
oral dyskinesia. Five monkeys had mild oral
tardive dyskinesia because of previous antagonist treatment. Interactions between the
dopamine (DA) D1 receptor agonist
SKF 81297 and the DA D2/D3 receptor agonist
quinpirole, DA D1 and D2 receptor antagonists, and the
anticholinergic biperiden were investigated.
SKF 81297, 0.3 mg/kg, induced acute
oral dyskinesia and grooming, which were each inhibited by the DA D1 receptor antagonist
NNC 756 in a dose-dependent manner. The DA D2 receptor antagonist
raclopride enhanced SKF 81297-induced acute
oral dyskinesia and suppressed SKF 81297-induced grooming, each with bell-shaped dose-effect curves.
Quinpirole, 0.1 mg/kg, induced a hyperarousal syndrome (i.e., increased arousal, stereotypy, and locomotion). Concomitant treatment with
SKF 81297 and
quinpirole caused an extreme hyperarousal syndrome but antagonized acute
oral dyskinesia and grooming, suggesting a synergistic effect of high-efficacy DA D1 and D2/D3 receptor agonists regarding the induction of the hyperarousal syndrome and the antagonism of acute
oral dyskinesia and grooming.
Biperiden, 0.25 mg/kg, antagonized both the SKF 81297-induced and
raclopride-induced acute
oral dyskinesia. The results suggest that
oral dyskinesia and grooming are independent but most often simultaneously occurring behaviors. Grooming is induced by DA D1 receptor agonists and antagonized by D1 and D2 antagonists and D2/D3 agonists. Acute
oral dyskinesia is induced by D1 agonists and lower doses of D2 antagonists, but antagonized by D1 antagonists, D2/D3 agonists, and
anticholinergics. These results suggest varying interactions between dopaminergic receptor subtypes in different types of dopaminergic behaviors.