Neurobiochemical changes in tardive dyskinesia.
There is evidence for the view that both up- and downregulation of nigral GABA may give rise to dyskinetic movements. Intranigral infusion of GABA agonists causes stereotyped licking and gnawing in rats, while intranigral GABA antagonists produce vacuous chewing movements. It is hypothesized that during long-term neuroleptic treatment there may be a succession of changes within striatonigral GABA neurons: down-regulation caused by neuroleptic drugs may increase receptor sensitivity, and this may lead to overcompensation and withdrawal dyskinesia during periods of cessation of drug treatment. Reduced nigral GAD activity may be a marker of irreversible brain damage and has not been observed in all chronic experiments, but only in individuals with long-standing or irreversible dyskinesia. Changes within the GABA system seem to be accompanied by changes in the striatal and nigral levels of substance P.
Gunne
L M
LM
Psychiatric Research Center, Ulleråker Hospital, Uppsala, Sweden.
Häggström
J E
JE
Johansson
P
P
Levin
E D
ED
Terenius
L
L
D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity; D001058:Apomorphine / Q000633:toxicity; D002428:Cebus; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000503:physiopathology*; D051381:Rats; D013373:Substance P / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D014150:Antipsychotic Agents; D013373:Substance P; D005680:gamma-Aminobutyric Acid; D001058:Apomorphine