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 t hey were challenged with the dopamine D1 receptor agonist SK&F 38393, either alone or after pretreatment with NNC-756. Neither treatment reg imen resulted in irreversible increases in oral activities when treate d rats were compared with controls; however, transient elevations were observed in the beginning of treatment in the continuously treated gr oup and in the withdrawal phase in the discontinuously treated group. Furthermore, discontinuous treatment resulted in within-group elevatio ns in vacuous chewing movements and tongue protrusions after withdrawa l. Dopamine D1 receptor supersensitivity was not observed after challe nge with the dopamine D1 receptor agonist. NNC-756 efficiently blocked the behavioural response to stimulation with SK&F 38393. Both treatme nt regimens resulted in the development of rigidity and catalepsy. The present study suggests that treatment with selective dopamine D1 rece ptor antagonists is less likely to cause irreversible oral dyskinesia than is treatment with classical neuroleptic drugs.