Effect of D1 and D2 agonists in primates withdrawn from long-term treatment with haloperidol: the potential role of dopamine D1 receptors in dyskinesia

Abstract

The effects of dopamine (DA) D1 and D2 receptor agonists were evaluated in eight Cebus apella monkeys. The monkeys had previously received haloperidol for 2 years, and five of the monkeys had developed mild oral dyskinesia. SKF 81297 (a full D1 agonist) induced marked oral hyperkinesia, consisting of tongue protrusions and licking or chewing movements, most pronounced in the monkeys with pre-existing oral dyskinesia. SKF 38393 and SKF 75670 (partial D1 agonists) also induced some oral dyskinesia, but to a lesser extent than SKF 81297, and with few licking movements. The partial D1 agonists, but not the full agonist, induced sedation. All of the D1 agonists induced grooming behavior, the full D1 agonist to the greatest extent. In the case of SKF 81297, the grooming was closely associated with the licking behavior. Quinpirole (a selective D2 agonist) and apomorphine (a mixed D1/D2 agonist) induced a hyperactive syndrome (nonoral stereotypy with rapid repetitive movements and increased arousal and locomotor activity). Quinpirole induced no grooming behavior and reduced pre-existing oral movements. The data indicate behavioral differences between D1 and D2 receptors and suggest that D1 receptors may be involved in the pathophysiology of some forms of dyskinesia syndromes.