Experimental tardive dyskinesia.
In ongoing studies of chronic administration of neuroleptics to monkeys (Cebus apella) and rats, the regional distribution of glutamic acid decarboxylase (GAD) and brain levels of homovanillic acid were examined. Reduction of GAD activity, a GABA-synthesizing enzyme, in three specific brain areas (substantia nigra, medial globus pallidus, and nucleus subthalamicus) was related to the development of neuroleptic induced dyskinesias; these reductions were not seen in treated animals who did not develop movement disorders. The neostriatal level of HVA was reduced in dyskinetic monkeys. Such animal models can be useful in the screening process for new antipsychotics and thus potentially aid in the prevention of drug-induced tardive dyskinesia.
Gunne
L M
LM
Häggström
J E
JE
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002428:Cebus; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004409:Dyskinesia, Drug-Induced / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology; D005476:Fluphenazine / Q000009:adverse effects / Q000494:pharmacology; D005625:Frontal Lobe / Q000187:drug effects / Q000201:enzymology; D005917:Globus Pallidus / Q000187:drug effects / Q000201:enzymology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006220:Haloperidol / Q000009:adverse effects / Q000494:pharmacology; D006719:Homovanillic Acid / Q000378:metabolism; D051381:Rats; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis / Q000502:physiology
D014150:Antipsychotic Agents; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; D006220:Haloperidol; D005476:Fluphenazine; D006719:Homovanillic Acid