State-dependent blockade of haloperidol-induced sensitization of catalepsy by MK-801.
NMDA receptor antagonists have been shown to block several forms of neural and behavioural plasticity. The prototypical and most widely-used noncompetitive NMDA receptor antagonist is dizocilpine (MK-801). Here we have examined the effect of MK-801 on the context-dependent augmentation ('sensitization') of catalepsy in rats which develops with repeated administration of haloperidol. It was found that over a 7-day treatment period animals receiving haloperidol (0.25 or 0.5 mg/kg) plus MK-801 (0.16 mg/kg) showed a context-dependent day-to-day increase in catalepsy similar to animals that received haloperidol alone. However, when all animals were treated with haloperidol alone on day 8 of the experiment, animals that had received haloperidol plus MK-801 before displayed a much smaller cataleptic response, similar to that observed in the haloperidol group on the first treatment day, i.e. the previously-established enhancement of catalepsy was no longer expressed. These results may be explained in terms of state-dependency effects induced by MK-801. Implications of these findings for the clinical use of NMDA receptor antagonists in the treatment of Parkinson's disease are discussed.
Schmidt
W J
WJ
University of Tübingen, Department of Neuropharmacology, Zoological Institute, Germany. werner.schmidt@uni-tuebingen.de
Tzschentke
T M
TM
Kretschmer
B D
BD
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced* / Q000503:physiopathology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000502:physiology; D006220:Haloperidol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D006220:Haloperidol