title: NR2B subunit blockade does not affect motor symptoms induced by 3-nitropropionic acid.
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.
authors.affiliation: Department of Experimental and Clinical Medicine, Section of Pharmacology, University of Ferrara, Italy. martina.fantin@epfl.ch
authors.forename: Martina
authors.initials: M
authors.lastname: Fantin
authors.forename: Michele
authors.initials: M
authors.lastname: Morari
authors.forename: François
authors.initials: F
authors.lastname: Tison
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Fernagut
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D006816:Huntington Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity; D009574:Nitro Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity*; D010636:Phenols / Q000494:pharmacology* / Q000627:therapeutic use; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D011422:Propionates / Q000037:antagonists & inhibitors / Q000633:toxicity*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D017211:Treatment Failure
chemical_list: D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; D009498:Neurotoxins; D009574:Nitro Compounds; D010636:Phenols; D010880:Piperidines; D011422:Propionates; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981; C015392:3-nitropropionic acid