Adaptations of NMDA and dopamine D-2, but not of muscarinic receptors following 14 days administration of uncompetitive NMDA receptor antagonists

Citation
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
Citations number
37
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEURAL TRANSMISSION
ISSN journal
03009564 → ACNP
Volume
106
Issue
5-6
Year of publication
1999
Pages
409 - 421
Database
ISI
SICI code
0300-9564(1999)106:5-6<409:AONADD>2.0.ZU;2-I
Abstract
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.