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Brain Res. 2015 Apr 7;1603:1-7. doi: 10.1016/j.brainres.2015.01.041. Epub 2015 Feb 2.

Memantine selectively blocks extrasynaptic NMDA receptors in rat substantia nigra dopamine neurons.

Author information

1
Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
2
Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA; Veterans Affairs Portland Health Care System, Portland, OR 97207, USA. Electronic address: johnsost@ohsu.edu.

Abstract

Recent studies suggest that selective block of extrasynaptic N-methyl-d-aspartate (NMDA) receptors might protect against neurodegeneration. We recorded whole-cell currents with patch pipettes to characterize the ability of memantine, a low-affinity NMDA channel blocker, to block synaptic and extrasynaptic NMDA receptors in substantia nigra zona compacta (SNC) dopamine neurons in slices of rat brain. Pharmacologically isolated NMDA receptor-mediated EPSCs were evoked by electrical stimulation, whereas synaptic and extrasynaptic receptors were activated by superfusing the slice with NMDA (10 ┬ÁM). Memantine was 15-fold more potent for blocking currents evoked by bath-applied NMDA compared to synaptic NMDA receptors. Increased potency for blocking bath-applied NMDA currents was shared by the GluN2C/GluN2D noncompetitive antagonist DQP-1105 but not by the high-affinity channel blocker MK-801. Our data suggest that memantine causes a selective block of extrasynaptic NMDA receptors that are likely to contain GluN2C/2D subunits. Our results justify further investigations on the use of memantine as a neuroprotective agent in Parkinson's disease.

KEYWORDS:

Brain slice; DQP-1105; Extrasynaptic; MK-801; Synaptic; Whole-cell recording

PMID:
25656790
DOI:
10.1016/j.brainres.2015.01.041
[Indexed for MEDLINE]

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