Mb. Hesselink et al., Adaptations of NMDA and dopamine D-2, but not of muscarinic receptors following 14 days administration of uncompetitive NMDA receptor antagonists, J NEURAL TR, 106(5-6), 1999, pp. 409-421
Behavioral changes have previously been reported following administrations
of uncompetitive NMDA receptor antagonists memantine, amantadine and MK-801
for 14 days, at the doses that produce plasma levels comparable to those s
een in patients (20, 100 and 0.31mg/kg/day respectively). Using the same do
ses, the effect on receptor binding (autoradiography) was studied in rats.
[H-3]MK-801 binding was increased in the dentate gyrus and CA3 region of th
e hippocampus (35.2 and 24.3% respectively) following 3 days S.C. infusion
of memantine by ALZET minipumps. One daily injection of memantine for 14 da
ys, increased [H-3]MK-801 binding in the frontal cortex by 40.3%. The same
treatment with amantadine did increase [H-3]raclopride binding to dopamine
D-2 receptors by 13.5%. None of these treatments changed the expression of
muscarinic receptors. It is concluded that subchronic blockade of the NMDA
receptor by uncompetitive antagonists at moderate (therapeutically-relevant
) doses induced only minor changes in NMDA and dopamine D-2 receptor expres
sion.