ACUTE HALOPERIDOL ATTENUATES THE HYPOMOTILITY INDUCED WITH 7-HYDROXY-DPAT

DOPAMINE D-3 receptors have been implicated in pathophysiological subs trates of schizophrenia, and neuroleptic drugs which are antagonists p rimarily at D-2 receptors possess therapeutic activity in this disorde r. In the present study, rats tested for hypomotility induced by 7-hyd roxy-DPAT (70H, a selective D-3 agonist) were pretreated with the neur oleptic haloperidol. These animals showed an attenuated agonist-induce d suppression of behavior compared with rats receiving 70H alone. The drug combination also 'normalized' dopamine metabolism in the frontal cortex, as turnover ratios which are typically enhanced by acute neuro leptic administration were no longer significantly increased when 70H was also given. These observations suggest that the effects of haloper idol in cortical regions regulating limbic locomotor systems may be im portant for therapeutic efficacy in schizophrenic symptoms generated f rom a D-3 substrate.