Lifelong Rodent Model of Tardive Dyskinesia-Persistence After Antipsychotic Drug Withdrawal.

摘要: Tardive dyskinesia (TD), first appearing in humans after introduction of the phenothiazine class antipsychotics 1950s, is now recognized as an abnormality resulting predominately by long-term block dopamine (DA) D2 receptors (R). TD thus reproduced primates and rodents chronic administration D2-R antagonists. Through a series studies since 1980s, it has been shown rodent modeling that when haloperidol or other antagonist added to drinking water, rats develop spontaneous oral dyskinesias, vacuous chewing movements (VCMs), ~3 months, this associated with increase number striatal D2-R. This persists for duration another ~2 months withdrawal. By neonatally lesioning dopaminergic nerves brain neonatal 6-hydroxydopamine (6-OHDA), found develops sooner, at also accompanied much higher VCMs these haloperidol-treated lesioned rats, lifelong withdrawal, but not increased haloperidol-withdrawn phase. apparently related part supersensitization both D1-R serotoninergic 5-HT2-R, which typical outcome 6-OHDA (n6-OHDA) lesioning. Testing during phase n6-OHDA displaying reveals receptor agonists antagonists host neuronal phenotypic classes have virtually no effect on VCM number, except 5-HT2-R acutely abate incidence part. Extrapolating human TD, appears (1) crucial alteration accounting persistence (2) dopaminergic—perhaps age-related partial denervation—is risk factor development (3) therapeutic potential alleviate particularly if/when antipsychotic blocker withdrawn.