A mechanism underlying neuroleptic induced oral dyskinesias in rats.
Previously we have found that spontaneous repetitive jaw movements (RJM) in rats can be augmented by dopamine D1 receptor stimulation and attenuated by D2 stimulation or by D1 blockade. We now report that high and low RJM responders can be inbred and that RJM responses in such rats are further augmented during washout from eight months of treatment with fluphenazine, a time when N-propyl-apomorphine induced stereotypy is severely depressed. Moreover, selective D1 receptor inactivation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) fails to reduce RJM. Therefore, D2 blockade by neuroleptics is deemed to be the most important mechanism for RJM enhancement. In conclusion, our studies show that oral behaviors are under genetic control, perhaps suggesting that the appearance of tardive dyskinesia in only some patients under neuroleptic therapy is due to a genetic disposition. Furthermore, tardive dyskinesia may be less likely to develop if the neuroleptics used are less potent against D2 receptors, as has been reported for some of the atypical antipsychotic drugs.
Rosengarten
H
H
Department of Psychiatry, New York University School of Medicine, New York 10016.
Schweitzer
J W
JW
Friedhoff
A J
AJ
D000704:Analysis of Variance; D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives / Q000494:pharmacology; D001552:Benzazepines; D015259:Dopamine Agents / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced; D005476:Fluphenazine / Q000008:administration & dosage / Q000633:toxicity*; D007568:Jaw; D008297:Male; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects
D001552:Benzazepines; D015259:Dopamine Agents; D065127:Dopamine D2 Receptor Antagonists; D011804:Quinolines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C009074:N-n-propylnorapomorphine; C000470:EEDQ; C071262:SK&F 82958; D001058:Apomorphine; D005476:Fluphenazine