The topography of the locomotor effects of haloperidol and domperidone

The neuroleptics are currently the primary mode of treatment for schizophrenia. Unfortunately, the study of the behavioral effects of these drugs has been hampered by inadequate methodology. Researchers have lacked means sensitive enough to detect the neuroleptic's spontaneous behavioral effects at low doses. Consequently, most previous studies have measured the ability of these drugs to block the effects of various dopamine agonists. In an attempt to remedy this, the present study employed one of the recently developed automated animal activity monitors. This system was used to measure the spontaneous nocturnal behavioral effects of the neuroleptic haloperidol (0.0, 0.1, 0.5, 1.0 mg/kg) on 12 male Sprague-Dawley rats. The behavioral effects of domperidone (0.0, 0.1, 0.5, 1.0 mg/kg) were also studied in order to compare the effects of central and peripheral dopamine antagonism. The results showed that haloperidol depressed all aspects of behavior studied--even at the lowest dose--while domperidone depressed only average speed. These results suggest that all of the locomotor variables studied, save average speed, are centrally mediated. Average speed, though influenced by central mechanisms, seems primarily a peripheral function.