Vacuous chewing movements in rats may be an animal analogue of the human motor disorder,
tardive dyskinesia. The movements are phenomenologically and pharmacologically similar to
tardive dyskinesia. The pathophysiology of these involuntary oral movements, and perhaps of
tardive dyskinesia, are likely to include both
dopamine receptor changes, and alterations in
GABA (
gamma-aminobutyric acid) system function. In an attempt to test the involvement of
GABA system dysfunction in these movements, we treated rats chronically with water alone,
haloperidol alone, the
GABA agonist progabide alone, and
haloperidol plus
progabide. Sprague-Dawley rats received
haloperidol (1.5 mg/kg per day) in their
drinking water and
progabide (100 mg/kg per day) in their food for 12 months. After 12 months of treatment,
haloperidol had induced vacuous chewing movements when administered alone, but the prevalence of the movements was decreased by 40% with the coadministration of
progabide. Moreover, the
haloperidol-
progabide-treated animals did not merely demonstrate movement suppression but actual inhibition of movement onset, as determined by an additional
progabide-withdrawal experiment. These data would suggest that
progabide and perhaps other GABAmimetic compounds can prevent the development of
tardive dyskinesia in man.