Intermittent versus continuous neuroleptic treatment in a rat model.

ABSTRACT

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.