Summary.
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 seen in patients (20, 100 and 0.31 mg/kg/day respectively). Using the same doses, the effect on receptor binding (autoradiography) was studied in rats. [3H]MK-801 binding was increased in the dentate gyrus and CA3 region of the 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 days, increased [3H]MK-801 binding in the frontal cortex by 40.3%. The same treatment with amantadine did increase [3H]raclopride binding to dopamine D2 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 D2 receptor expression.
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Received September 18, 1998; accepted November 16, 1998
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Hesselink, M., De Boer, A., Breimer, D. et al. Adaptations of NMDA and dopamine D2, but not of muscarinic receptors following 14 days administration of uncompetitive NMDA receptor antagonists. J Neural Transm 106, 409–421 (1999). https://doi.org/10.1007/s007020050168
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DOI: https://doi.org/10.1007/s007020050168