Rat model of tardive dyskinesia gets boost.

Rat model of tardive dyskinesia gets boost

In the last decade, researchers have tried in vain to come up with a plausible animal model of tardive dyskinesia (TD), an often disabling potpourri of abnormal body movements afflicting about one in five people treated for extended periods with antipsychotic drugs (SN: 7/20/85, p.45). Rats and monkeys sometimes develop the twitches and jerks typical of TD when given antipsychotics, but there is no consensus that their reactions consistently mimic those of humans with the disorder.

Now, however, two psychologists claim they have developed a strong candidate for a rat model of TD with the aid of computerized measurements of the animals' mouth movements. "These findings are going to revolutionize rodent research on antipsychotic-induced side effects," says study director Gaylord Ellison of the University of California, Los Angeles. He and his co-worker Ronald E. See expect publication of their results in a forthcoming PSYCHOPHARMACOLOGY.

Other investigators are encouraged by the new findings but refuse to hail them as revolutionary. "This area of research has been dogged by the inability of different laboratories to replicate findings," says psychopharmacologist John L. Waddington of the Royal College of Surgeons in Dublin, Ireland. "Ellison's work is provocative, but it clearly needs to be examined further by other scientists."

The California researchers administered equivalent doses of the antipsychotic drug haloperidol to two groups of rats for 28 days and to another two groups for eight months. One group on each time schedule received weekly haloperidol injections: the other two groups received the drug continuously in their drinking water and, in the eighth month of long-term treatment, through a small pump implanted in each rat as well.

Mouth movements made by the rats were regularly measured during drug treatment and up to 17 days after drug administration ended. Each rat was placed in a tube for video recording with a spot of ultraviolet-sensitive ink on its upper and lower lip. All lights were turned out save for a black light. The research team used a specially designed computer program that calculated the energy spectrum of oral movements to analyze video images of the lip spots.

The two groups of rats given antipsychotics for eigth months gradually developed abnormal mouth movements with different properties, Ellison and See report. After four months of treatment, rats on the continuous schedule did not necessarily develop more frequent or more easily observable mouth movements. But computer analysis revealed a characteristic altered form to the movements, with the peak energy frequency at 1 to 3 hertz. Several recent studies reported observing this same altered frequency in humans with tardive dyskinesia, Ellison notes.

Rats given weekly drug injections developed larger, gaping mouth movements at energy frequencies between 4 and 7 hertz. Their responses are somewhat similar to temporary movement disorders distinct from TD observed in monkeys and humans administered antipsychotics, Ellison notes.

If continuous haloperidol treatment does produce TD in rats, researchers can use the animals to study the side effects of other antipsychotics and to test potential drug treatments for TD.

But it remains unclear whether Ellison and See's model applies to humans, cautions Daniel E. Casey of the Veterans Administration Medical Center in Portland, Ore. No one knows how long drug-induced abnormal mouth movements perist in rats, he says, and the movements are far less obvious and widespread than those of humans with TD.

The peak energy frequency of human TD movements is not well established, Casey adds.