Effects of chronic discontinuous and continuous treatment of rats with a dopamine D1 receptor antagonist (NNC-756).

Rats were treated intermittently or continuously with the dopamine D1 receptor antagonist NNC-756 for 15 weeks. Two weeks after withdrawal they were challenged with the dopamine D1 receptor agonist SK&F 38393, either alone or after pretreatment with NNC-756. Neither treatment regimen resulted in irreversible increases in oral activities when treated rats were compared with controls; however, transient elevations were observed in the beginning of treatment in the continuously treated group and in the withdrawal phase in the discontinuously treated group. Furthermore, discontinuous treatment resulted in within-group elevations in vacuous chewing movements and tongue protrusions after withdrawal. Dopamine D1 receptor supersensitivity was not observed after challenge with the dopamine D1 receptor agonist. NNC-756 efficiently blocked the behavioural response to stimulation with SK&F 38393. Both treatment regimens resulted in the development of rigidity and catalepsy. The present study suggests that treatment with selective dopamine D1 receptor antagonists is less likely to cause irreversible oral dyskinesia than is treatment with classical neuroleptic drugs.