The relationship between oral dyskinesias produced by long-term haloperidol treatment, the density of striatal preproenkephalin messenger RNA and enkephalin peptide, and the number of striatal neurons expressing preproenkephalin messenger RNA in rats.
Neuroleptic-induced oral dyskinesias in rats, a putative analogue to human tardive dyskinesia, may be due to excitotoxic degeneration within the striatum. Haloperidol treatment for 34 weeks increased the optical density of preproenkephalin messenger RNA in individual striatal neurons and enkephalin peptide in the neuropil, regardless of the level of oral dyskinesia produced. However, using unbiased stereological methods, an increased number of striatal neurons expressing preproenkephalin messenger RNA was observed only in rats that did not develop pronounced oral dyskinesias during haloperidol treatment. Said in another manner, the haloperidol-treated animals that developed pronounced oral dyskinesias, failed to produce an increase in the number of neurons expressing preproenkephalin messenger RNA. These results indicate that the mechanism by which neuroleptics induce oral dyskinesias in rats, and perhaps tardive dyskinesia in humans, involves a functional disturbance or even damage to a subpopulation of enkephalinergic neurons in the striatum.
Department of Physiology, University of Bergen, Norway.
O A
OA
Andreassen
B
B
Finsen
K
K
Ostergaard
J C
JC
Sørensen
M J
MJ
West
H A
HA
Jørgensen
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D004745:Enkephalins / Q000235:genetics*; D005207:Fasciculation; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology*; D006801:Humans; D009043:Motor Activity; D009055:Mouth; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic / Q000187:drug effects*; D014743:Videotape Recording
D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; C033660:preproenkephalin; D006220:Haloperidol