A mechanism underlying neuroleptic induced oral dyskinesias in rats.

Abstract	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.
Authors	H Rosengarten, J W Schweitzer, A J Friedhoff
Journal	Polish journal of pharmacology (Pol J Pharmacol) 1993 Jul-Aug Vol. 45 Issue 4 Pg. 391-8 ISSN: 1230-6002 [Print] Poland
PMID	7906991 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Benzazepines Dopamine Agents Dopamine D2 Receptor Antagonists Quinolines Receptors, Dopamine D1 Receptors, Dopamine D2 N-n-propylnorapomorphine EEDQ SK&F 82958 Apomorphine Fluphenazine
Topics	Analysis of Variance Animals Apomorphine (analogs & derivatives, pharmacology) Benzazepines Dopamine Agents (pharmacology) Dopamine D2 Receptor Antagonists Dose-Response Relationship, Drug Dyskinesia, Drug-Induced Fluphenazine (administration & dosage, toxicity) Jaw Male Quinolines (pharmacology) Rats Rats, Sprague-Dawley Receptors, Dopamine D1 (antagonists & inhibitors, drug effects) Receptors, Dopamine D2 (drug effects) Stereotyped Behavior (drug effects)

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