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 neuroteptic 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 finding 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 administration.