Behavioural effects of dopamine D-1 and D-2 receptor agonists in monkeys previously treated with haloperidol.

The effects of dopamine D-1 and D-2 receptor agonists were evaluated in five Cebus apella monkeys. During a previous haloperidol treatment (2 years), three of the monkeys had developed oral tardive dyskinesia (tongue protrusion and/or chewing). The partial D-1 agonist, SKF 38393, induced/aggravated oral dyskinesia and slight sedation, but no non-oral repetitive movements. Conversely, the selective D-2 agonist, LY 171555, produced non-oral repetitive movements and increased reactivity (arousal), but no significant change in the oral movements. Apomorphine (a mixed D-1/D-2 agonist) induced non-oral repetitive movements, increased reactivity, and increased oral dyskinesia. Pretreatment with SKF 38393 inhibited the LY 171555-induced non-oral repetitive movements, while in four monkeys the SKF 38393-induced oral movements were inhibited by LY 171555. The results suggest that oral dyskinesia (tardive dyskinesia) is more related to D-1 receptor stimulation than to D-2 receptor supersensitivity.