Scopolamine fails to diminish chronic haloperidol-induced purposeless chewing in rats

Chronic haloperidol treatment for 4-12 months gradually induces spontaneous , irregular, purposeless oral chewing movements (CMs), apparently involunta ry, in some but not all treated rats. Based on phenomenologic and pharmacol ogic similarities, this laboratory preparation has been used as an animal m odel of tardive dyskinesia (TD), which is the human hyperkinetic motor synd rome associated with chronic antipsychotic administration. This putative an imal model has received the most severe challenge to its validity by claims that its oral movements can be suppressed by anticholinergic treatments, s ince resistance to anticholinergic suppression is an accepted pharmacologic feature of TD. In this experiment, we challenged a group of haloperidol-tr eated rats with CMs using three doses of scopolamine (0.1, 0.3, 1.0 mg/kg) and placebo and rated the change in dyskinetic movements. Each scopolamine dose reduced CMs by a similar magnitude, without any dose effect; the salin e dose also reduced CMs to an equivalent degree. Therefore, we concluded th at some component of the experiment, not the scopolamine, reduced the CMs. The handling component of the procedure was identified as a likely confound , and we tested this further. Rats with CMs were handled at several levels of "severity"; and the dyskinesias were rated at 1 and 3 h later. CMs were reduced by the experimental handling, in relation to the strength of the ha ndling. Minimal handling produced modest CM reductions with quick recovery; whereas, the "strongest" handling plus the placebo injection produced the greatest CM reduction, evident over 3 h, resembling the CM reductions seen in the scopolamine and placebo experiment. Overall, these results suggest t hat anticholinergic drugs do not suppress chronic haloperidol-induced rat C Ms. However, the movements are sensitive to stressful handling situations, and diminish with stress. In both of these characteristics, rat CMs resembl e human TD, further supporting a role for this model in studies of human TD .