Numerous data indicate that noncompetitive and competitive
N-methyl-D-aspartate (
NMDA) receptor antagonists inhibit the development of physical dependence on
opioids when these substances are administered together, and
NMDA receptor antagonists are used at lower range of doses. Higher doses of these antagonists can enhance some
opioid-induced effects. The present study extends these findings to the effects of
NMDA/
glycine (
glycine(B)) site antagonists. Wistar rats were rendered dependent on
morphine by implantation of
morphine pellets. Both of the
glycine(B) site antagonists used, 7-chloro-4-hydroxy-3-(3-phenoxy)-phenyl-2(H)-quinolone (
L-701,324; 2.5 and 5.0 mg/kg) and
5,7-dichlorokynurenic acid (5,7-DCKA; 25, 50, and 100 mg/kg), suppressed the expression of
morphine withdrawal syndrome estimated as wet dog shakes. Furthermore,
L-701,324 (2.5 and 5 mg/kg), given twice a day during the development of
morphine dependence, attenuated the development of
morphine dependence, and the results were comparable to those obtained after administration of noncompetitive
NMDA receptor antagonist -
MK801 (0.1 mg/kg). Our data suggest that
glycine(B) site antagonists may attenuate wet dog shakes (withdrawal) and the development of dependence, both being induced by chronic
morphine administration in rats.