Dopamine D(1A) receptor function in a rodent model of tardive dyskinesia

Tardive dyskinesia develops as a common complication of long-term neuroleptic use. The emergence of such dyskinesias may reflect a shift in the balance of dopamine D(1) and D(2) receptor-mediated activity, with a relative increase in activity in the D(1) receptor-regulated direct striatonigral pathw...

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Bibliographic Details
Published in:Neuroscience 2000, Vol.101 (3), p.629
Main Authors: Van Kampen, J M, Stoessl, A J
Format: Article
Language:English
Subjects:
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine - pharmacology
Animals
Antipsychotic Agents - adverse effects
Behavior, Animal - drug effects
Behavior, Animal - physiology
Binding Sites - drug effects
Binding Sites - physiology
Disease Models, Animal
Dopamine Agonists - pharmacology
Dyskinesia, Drug-Induced - metabolism
Dyskinesia, Drug-Induced - pathology
Dyskinesia, Drug-Induced - physiopathology
Fluphenazine - pharmacology
Male
Mastication - drug effects
Mastication - physiology
Neostriatum - drug effects
Neostriatum - pathology
Neostriatum - physiopathology
Neurons - drug effects
Neurons - metabolism
Neurons - pathology
Raclopride - pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Dopamine D1 - drug effects
Receptors, Dopamine D1 - genetics
Receptors, Dopamine D1 - metabolism
Receptors, Dopamine D2 - drug effects
Receptors, Dopamine D2 - metabolism
RNA, Messenger - drug effects
RNA, Messenger - metabolism
Tritium
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Summary:Tardive dyskinesia develops as a common complication of long-term neuroleptic use. The emergence of such dyskinesias may reflect a shift in the balance of dopamine D(1) and D(2) receptor-mediated activity, with a relative increase in activity in the D(1) receptor-regulated direct striatonigral pathway. In rats, chronic treatment with the antipsychotic fluphenazine triggers a syndrome of vacuous chewing movements, which are attenuated by dopamine D(1) receptor antagonists. A similar syndrome can be seen in drug-naive animals following acute administration of selective dopamine D(1) receptor agonists. However, not all dopamine D(1) receptor agonists elicit these mouth movements. Thus, some investigators have suggested the existence of novel subtypes of the dopamine D(1) receptor. In these studies, we sought to clarify the role of the dopamine D(1A) receptor in vacuous chewing movements induced both by the selective dopamine D(1) receptor agonist SKF 38393, as well as by chronic neuroleptic administration, using in vivo oligonucleotide antisense to dopamine D(1A) receptor messenger RNA. Intrastriatal antisense treatment significantly and selectively attenuated striatal dopamine D(1) receptor binding, accompanied by reductions in SKF 38393- and chronic fluphenazine-induced vacuous chewing movements. These findings suggest that the dopamine D(1A) receptor plays an important role in the expression of vacuous chewing movements in a rodent model of tardive dyskinesia and may contribute to the pathogenesis of the human disorder. This may have important implications for the treatment of tardive dyskinesia in humans.
ISSN:0306-4522
1873-7544
DOI:10.1016/S0306-4522(00)00412-7