Intermittent versus continuous neuroleptic treatment in a rat model.
The treatment schedule for neuroleptic therapy is of relevance when evaluating the development of side-effects. Seventy-five rats were treated discontinuously or continuously with the predominantly dopamine D2 receptor blocker haloperidol or the combined dopamine D1/D2 receptor blocker zuclopenthixol for 15 weeks. During and after treatment, a broad spectrum of behavioural parameters including vacuous chewing movements and tongue protrusions were observed. Discontinuous neuroleptic treatment as opposed to continuous neuroleptic treatment produced a significant long-lasting increase in oral activity. The changes were most pronounced in haloperidol-treated rats. The differences observed may have methodological implications for animal models of neuroleptic-induced movement disorders. Our findings are consistent with the hypothesis that pharmacological sensitization to the dyskinetic side-effects of neuroleptics develops when the drug effect is allowed to wear off between repeated administrations.
Glenthøj
B
B
Department of Psychiatry, Rigshospitalet, University of Copenhagen, Denmark.
Hemmingsen
R
R
Allerup
P
P
Bolwig
T G
TG
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003006:Clopenthixol / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D004409:Dyskinesia, Drug-Induced / Q000209:etiology; D006220:Haloperidol / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008409:Mastication; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains
D003006:Clopenthixol; D006220:Haloperidol