Haloperidol potentiates the EEG slowing of MK-801 despite blocking its motor effects: implications for the PCP model of schizophrenia.
Haloperidol (HP) can block both the motor stimulation and the neurotoxic vacuolization of MK-801, suggesting that the two drugs have antagonistic brain actions. However, we show here that the modest EEG slowing produced by HP and MK-801 individually is massively potentiated when the drugs are combined. This finding challenges the argument for the PCP model of schizophrenia that assumes a general antagonism of neuroleptics and NMDA channel blockers. It further suggests that blockade of MK-801 motor effects is an inadequate test for antipsychotic drug actions. Our data indicate that intact function of D2 receptors (or other HP targets) is required to prevent generalized EEG slowing in the presence of NMDA channel blockade, a possibility of potential clinical interest.
Feinberg
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Department of Psychiatry, University of California, Davis 95616, USA.
Campbell
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D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004569:Electroencephalography / Q000187:drug effects*; D004576:Electromyography / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006213:Hallucinogens; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010622:Phencyclidine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D012895:Sleep, REM / Q000187:drug effects
D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D006213:Hallucinogens; D016291:Dizocilpine Maleate; D010622:Phencyclidine; D006220:Haloperidol