Reversibility and irreversibility of tardive dyskinesia following neuroleptic withdrawal

Lahti, Adrienne C.; Thaker, Gunvant K.; Moran, Martin J.; Tamminga, C.A.

doi:10.1016/0920-9964(92)90165-2

Cited by 2 publications

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“…No treatment or prophylaxis for TD is currently available. The disorder has a gradual onset, and remains expressed after withdrawal of the antipsychotic for some prolonged period of time even though not always permanently (Tarsy and Baldessarini 1974;Lahti et al 1988). In humans, tardive dyskinetic movements are resistant to anticholinergic suppression, distinguishing these tardive movements from hypokinetic parkinsonian movements that regularly diminish with anticholinergic treatment (Gerlach et al 1974;Klawans and Rubovits 1974;Casey and Denney 1977).…”

Section: Introductionmentioning

confidence: 98%

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

2001

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Chronic haloperidol treatment for 4-12 months gradually induces spontaneous, irregular, purposeless oral chewing movements (CMs), apparently involuntary, in some but not all treated rats. Based on phenomenologic and pharmacologic similarities, this laboratory preparation has been used as an animal model of tardive dyskinesia (TD), which is the human hyperkinetic motor syndrome associated with chronic antipsychotic administration. This putative animal model has received the most severe challenge to its validity by claims that its oral movements can be suppressed by anticholinergic treatments, since resistance to anticholinergic suppression is an accepted pharmacologic feature of TD. In this experiment, we challenged a group of haloperidol-treated 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 saline dose also reduced CMs to an equivalent degree. Therefore, we concluded that 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 handling. 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 that anticholinergic drugs do not suppress chronic haloperidol-induced rat CMs. However, the movements are sensitive to stressful handling situations, and diminish with stress. In both of these characteristics, rat CMs resemble human TD, further supporting a role for this model in studies of human TD.

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