W. Zajaczkowski et al., DISCRIMINATIVE STIMULUS EFFECTS OF THE NMDA RECEPTOR ANTAGONISTS MK-801 AND CGP-37849 IN RATS, Pharmacology, biochemistry and behavior, 55(1), 1996, pp. 163-168
Rats were trained to discriminate MK-801 (0.05 mg/kg, IF), an uncompet
itive, or CGP 37849 (3 mg/kg, IF), a competitive NMDA receptor antagon
ist from saline, using a two-lever, operant drug discrimination paradi
gm. In generalization tests the role of dopaminergic and serotonergic
systems in the discriminative stimulus effects produced by both NMDA r
eceptor antagonists was studied with amphetamine (0.5 mg/kg), cocaine
(5.0 and 7.5 mg/kg), and fenfluramine (2.5 and 5.0 mg/kg). Additionall
y; memantine (5.0, 7.5 and 10.0 mg/kg), an uncompetitive NMDA receptor
antagonist, was tested. The discriminative stimuli produced by MK-801
and CGP 37849 were not generalized to each other. Among the tested dr
ugs only memantine generalized to the MK-801 discriminative stimulus.
None of the tested drugs showed CGP 37849-like discriminative stimulus
properties. The different mechanisms underlying NMDA antagonism by MK
-801 and GP 37849 might explain the observed lack of crossgeneralizati
on. The results suggest that dopaminergic and serotonergic systems are
not of major importance in the discriminative stimulus effects produc
ed by both MK-801 and CCP 37849.