The pathophysiologic basis of tardive dyskinesia.
The prolonged course of tardive dyskinesia (TD) associated with antipsychotic drugs suggests that permanent structural alterations of the brain occur, though neurohistopathological studies have provided little to support this view. An alternative view is that functional adaptive changes may account for the manifestations of TD. A currently popular hypothesis is that there may be a functional excess in the activity of dopamine (DA) as a synaptic neurotransmitter in the basal ganglia. A cholinergic mechanism has also been implicated in TD, but the clinical effects of acetylcholine agonists and antagonists in TD are variable. In animals, nigrostriatal neurons respond to the blockade of DA synapses by treatment with antipsychotic agents in several ways, including acute and transient increases in the turnover of DA, and more slowly evolving "disuse" supersensitivity, possibly of postsynaptic receptors. The latter effects have been studied extensively in animal models of presumably DA-mediated behavior, by chemical studies of DA-sensitive adenylate cyclase in caudate nucleus in vitro, and by studies of labeled dopamine receptors. The phenomenon of DA-supersensitivity might help to explain some of the acute "withdrawal dyskinesias" that follow the abrupt discontinuation of high doses of antipsychotic agents, and might contribute to other reversible forms of the syndrome, but may be too short-lived to explain the persistent forms of TD. It must be concluded that an explanation of the latter syndrome of persistent drug-related TD remains uncertain.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D003714:Denervation; D004298:Dopamine / Q000378:metabolism; D004409:Dyskinesia, Drug-Induced / Q000473:pathology / Q000503:physiopathology*; D004569:Electroencephalography; D009410:Nerve Degeneration; D009433:Neural Inhibition / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D014149:Tranquilizing Agents / Q000009:adverse effects
D011954:Receptors, Dopamine; D014149:Tranquilizing Agents; D004298:Dopamine