title: The NR2B antagonist, ifenprodil, corrects the l-DOPA-induced deficit of bilateral movement and reduces c-Fos expression in the subthalamic nucleus of hemiparkinsonian rats.
abstract: The use of NR2B antagonists in Parkinsonism is still controversial. To examine their anti-parkinsonian effects, the NR2B antagonist, ifenprodil, and L-DOPA were administered together and separately in hemiparkinsonian rats (hemi-PD) that were subjected to a cylinder test. Recovery from hypoactivity was achieved by single administration of 3-7 mg/kg of L-DOPA; however, improvement in the deficit of bilateral forelimb use was not observed. When administered alone, ifenprodil had no anti-parkinsonian effects; however, combined administration of ifenprodil and 7 mg/kg of L-DOPA significantly reversed the deficit of bilateral forelimb use without adversely affecting the L-DOPA-induced improvement in motor activity. Next, in order to identify the brain area influenced by L-DOPA and ifenprodil, quantitative analysis of L-DOPA-induced c-Fos immunoreactivity was performed in various brain areas of hemi-PD following administration of L-dopa with and without ifenprodil. Among brain areas with robust c-Fos expression within the motor loop circuit in dopamine-depleted hemispheres, co-administered ifenprodil markedly attenuated L-DOPA-induced c-Fos expression in only the subthalamic nucleus (STN), suggesting that the STN is the primary target for the anti-parkinsonian action of NR2B antagonists.
authors.affiliation: Division of Brain Science, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Japan. Electronic address: mi07511r@gmail.com.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Igarashi
authors.affiliation: Division of Brain Science, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Japan; Department of Occupational Therapy, School of Allied Health Sciences, Kitasato University, Sagamihara, Japan. Electronic address: habata@kitasato-u.ac.jp.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Habata
authors.affiliation: Division of Brain Science, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Japan; Department of Physiology, School of Allied Health Sciences, Kitasato University, Sagamihara, Japan. Electronic address: akita310@ahs.kitasato-u.ac.jp.
authors.forename: Hisanao
authors.initials: H
authors.lastname: Akita
authors.affiliation: Department of Physiology, School of Allied Health Sciences, Kitasato University, Sagamihara, Japan. Electronic address: noda1219@ahs.kitasato-u.ac.jp.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Noda
authors.affiliation: Department of Physiology, School of Allied Health Sciences, Kitasato University, Sagamihara, Japan. Electronic address: masa422@ahs.kitasato-u.ac.jp.
authors.forename: Masanori
authors.initials: M
authors.lastname: Ogata
authors.affiliation: Division of Brain Science, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Japan; Department of Physiology, School of Allied Health Sciences, Kitasato University, Sagamihara, Japan. Electronic address: sajim@ahs.kitasato-u.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Saji
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D005552:Forelimb; D007980:Levodopa / Q000008:administration & dosage*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000517:prevention & control*; D010880:Piperidines / Q000008:administration & dosage*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D020531:Subthalamic Nucleus / Q000187:drug effects / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; C121001:NR2B NMDA receptor; D010880:Piperidines; D016760:Proto-Oncogene Proteins c-fos; D016194:Receptors, N-Methyl-D-Aspartate; D007980:Levodopa; C010739:ifenprodil
keywords: Bilateral movement; Cylinder test; Parkinson's disease; Striatum; Subthalamic nucleus; l-DOPA