The rat model of tardive dyskinesia: Relationship between vacuous chewing movements and gross motor activity during acute and long-term haloperidol treatment

Abstract

Tardive dyskinesia (TD) is a serious side-effect of neuroleptic treatment. In order to describe and analyse more thoroughly the rat model of TD, the behavior of the rats during cage testing was studied after acute and during long-term haloperidol (HAL) treatment. Rats were injected with HAL IP in an acute experiment, and in a long-term experiment, rats were treated for 4 –12 months with HAL decanoate IM. Control rats received saline or sesame oil. The behavior was videotaped one h after the IP injection in the acute experiment, and at intervals during the long-term experiment. The putative TD analogue vacuous chewing movements (VCM), the general behavior and the type of behavior occurring simultaneously with VCM, were scored. Long-term (> 4 months) HAL treatment increased VCM but did not change the general behavior. The single IP injection of HAL markedly reduced locomotion in addition to increasing VCM. Both in the acute and in the long-term experiment, VCM appeared more frequently when the gross motor activity was low, indicating an intrinsic incompatibility between gross motor activity and VCM. However, in the long-term experiment, the distribution of VCM in the different categories of behavior was the same in OIL and HAL treated rats. This shows that cage-observed VCM in rats induced by long-term HAL treatment cannot be an artifact due to reduced locomotion. Thereby, an important argument against cage-observed VCM as a rat model of TD seems to be disproved.