Acute haloperidol attenuates the hypomotility induced with 7-hydroxy-DPAT.
Dopamine D3 receptors have been implicated in pathophysiological substrates of schizophrenia, and neuroleptic drugs which are antagonists primarily at D2 receptors possess therapeutic activity in this disorder. In the present study, rats tested for hypomotility induced by 7-hydroxy-DPAT (7OH, a selective D3 agonist) were pretreated with the neuroleptic haloperidol. These animals showed an attenuated agonist-induced suppression of behavior compared with rats receiving 7OH alone. The drug combination also 'normalized' dopamine metabolism in the frontal cortex, as turnover ratios which are typically enhanced by acute neuroleptic administration were no longer significantly increased when 7OH was also given. These observations suggest that the effects of haloperidol in cortical regions regulating limbic locomotor systems may be important for therapeutic efficacy in schizophrenic symptoms generated from a D3 substrate.
Lynch
M R
MR
Research and Development Service, Veterans Administration Medical Center, Syracuse, NY, USA.
Ormsby
J L
JL
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D008032:Limbic System / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013764:Tetrahydronaphthalenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D013764:Tetrahydronaphthalenes; D015102:3,4-Dihydroxyphenylacetic Acid; D006220:Haloperidol; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; D004298:Dopamine; D006719:Homovanillic Acid