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.