Broad-spectrum N-methyl D-aspartate (NMDA) antagonists, although proposed in therapies for several pathologies including Huntington's disease (HD), can produce dramatic side-effects. Thus, the therapeutic potential of subunit selective NMDA receptor antagonists warrants investigation. Overactivation of NMDA receptors containing the NR2B subunit plays a pathogenic role in HD, suggesting a neuroprotective potential of selective NR2B blockade. In the present study, we investigated whether the selective NR2B receptor antagonist, R-(R*,S*)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidinepropanol, could also affect motor symptoms in mice intoxicated with 3-nitropropionic acid (3-NP), a phenotypic model of HD. NR2B subunit acute blockade had no effect on spontaneous activity, HD-like symptoms (clinical scale), and sensorimotor performances (beam task) in 3-NP intoxicated mice. These results suggest that selective NR2B antagonism has no acute symptomatic effect on motor and sensorimotor impairments due to 3-NP-induced striatal injury. © W. S. Maney & Son Ltd 2011.
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Data di pubblicazione: | 2011 | |
Titolo: | NR2B subunit blockade does not affect motor symptoms induced by 3-nitropropionic acid | |
Autori: | Fantin, Martina; Morari, Michele; Tison, F.; Fernagut, P. | |
Rivista: | NEUROLOGICAL RESEARCH | |
Parole Chiave: | 3-nitropropionic acid; Motor behavior; NMDA; NR2B antagonist; NR2B subunit; Ro 25-6981; | |
Abstract: | Broad-spectrum N-methyl D-aspartate (NMDA) antagonists, although proposed in therapies for several pathologies including Huntington's disease (HD), can produce dramatic side-effects. Thus, the therapeutic potential of subunit selective NMDA receptor antagonists warrants investigation. Overactivation of NMDA receptors containing the NR2B subunit plays a pathogenic role in HD, suggesting a neuroprotective potential of selective NR2B blockade. In the present study, we investigated whether the selective NR2B receptor antagonist, R-(R*,S*)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidinepropanol, could also affect motor symptoms in mice intoxicated with 3-nitropropionic acid (3-NP), a phenotypic model of HD. NR2B subunit acute blockade had no effect on spontaneous activity, HD-like symptoms (clinical scale), and sensorimotor performances (beam task) in 3-NP intoxicated mice. These results suggest that selective NR2B antagonism has no acute symptomatic effect on motor and sensorimotor impairments due to 3-NP-induced striatal injury. © W. S. Maney & Son Ltd 2011. | |
Digital Object Identifier (DOI): | 10.1179/1743132810Y.0000000002 | |
Handle: | http://hdl.handle.net/11392/1691723 | |
Appare nelle tipologie: | 03.1 Articolo su rivista |