The mitochondrial toxin 3-nitropropionic acid induces vacuous chewing movements in rats. Implications for tardive dyskinesia?

Rats were chronically treated for 4 weeks with three doses (4, 8, 12 mg/kg per day) of the mitochondrial toxin 3-nitropropionic acid (3-NP). The behaviour was videotaped at intervals during and after treatment, and vacuous chewing movements (VCM), a putative analogue to tardive dyskinesia (TD), as well as the general behaviour were scored. During treatment, 3-NP dose-dependently increased VCM and dose-dependently reduced motor activity, which is similar to the behavioural effect of long-term neuroleptic treatment. The results may support the hypothesis that neuroleptic-induced impairment of energy metabolism, a potential excitotoxic mechanism, is involved in the development of VCM in rats and probably TD in humans.