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.