State-dependent blockade of haloperidol-induced sensitization of catalepsyby MK-801

NMDA receptor antagonists have been shown to block several forms of neural and behavioural plasticity. The prototypical and most widely-used noncompet itive NMDA receptor antagonist is dizocilpine (MK-801). Here we have examin ed the effect of MK-801 on the context-dependent augmentation ('sensitizati on') of catalepsy in rats which develops with repeated administration of ha loperidol. It was found that over a 7-day treatment period animals receivin g 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 receive d haloperidol alone. However, when all animals were treated with haloperido l alone on day 8 of the experiment, animals that had received haloperidol p lus 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. T hese results may be explained in terms of state-dependency effects induced by MK-801. Implications of these findings for the clinical use of NMDA rece ptor antagonists in the treatment of Parkinson's disease are discussed.