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Dyskinesia: animal experimental correlates
Abstract:
The results of behavioral studies in animals, which demonstrate increased effects of DA agonists after stopping chronic administration of neuroleptics, are consistent with an increased sensitivity of postsynaptic receptor and effector mechanisms in response to chronic disruption of DA transmission (disuse supersensitivity of DA receptors, see review by Moore & Thornburg (1975)). Although this mechanism may be responsible for the reversible withdrawal dyskinesias, it is probably not involved in persistent tardive dyskinesia. The persistence of the latter dyskinesias suggests an irreversible structural or chemical change, but with the exception of a report by Christensen et al. (1970) there is little evidence of neuroleptic-induced degenerative changes in the brains of man or animals. Although the etiology of tardive dyskinesias remains a mystery, pharmacological evidence suggests a functional overactivity of extrapyramidal mechanisms mediated by DA. To date, however, experiments with animal models have not provided a logical explanation for this overactivity.
Insights
Neuroleptic withdrawal can cause reversible movement disorders due to dopamine receptor supersensitivity. However, persistent tardive dyskinesia likely involves irreversible changes, with dopamine system overactivity suspected but not fully explained by current animal models.
Area of Science:
- Neuropharmacology
- Movement Disorders
Background:
- Chronic neuroleptic administration can lead to changes in dopamine (DA) transmission.
- Abrupt cessation of neuroleptics in animal models shows increased DA agonist effects, suggesting receptor supersensitivity.
Purpose of the Study:
- To investigate the mechanisms underlying reversible withdrawal dyskinesias and persistent tardive dyskinesia.
- To explore the role of dopamine (DA) system overactivity in extrapyramidal disorders.
Main Methods:
- Review of behavioral studies in animals.
- Analysis of pharmacological evidence regarding dopamine (DA) pathways.
- Examination of existing literature on neuroleptic-induced brain changes.
Main Results:
- Disuse supersensitivity of DA receptors may explain reversible withdrawal dyskinesias.
- Persistent tardive dyskinesia is unlikely solely due to receptor supersensitivity, suggesting irreversible changes.
- Limited evidence for neuroleptic-induced degenerative brain changes exists.
Conclusions:
- The etiology of tardive dyskinesia remains unclear.
- Pharmacological data point to functional overactivity in DA-mediated extrapyramidal mechanisms.
- Current animal models do not fully explain the observed overactivity in tardive dyskinesia.
