title: In vivo presynaptic and postsynaptic striatal dopamine functions in idiopathic normal pressure hydrocephalus.
abstract: Differentiation of impaired gait seen in idiopathic normal pressure hydrocephalus (iNPH) from parkinsonian gait is sometimes a great challenge and important for future medication in the clinical setting. To investigate dopaminergic contribution to its pathophysiology, two aspects of the trans-synaptic dopamine functions in the striatal region in eight iNPH patients naïve to dopaminergic drugs were examined using positron emission tomography with a presynaptic marker [11C]CFT ([11C]2-beta-carbomethoxy-3beta-(4-fluorophenyl) tropane) that binds to dopamine transporter and a postsynaptic marker [11C]raclopride that binds to D2 receptor. Quantitative values of binding potentials (BPs) for [11C]CFT and [11C]raclopride were compared between patients and eight age-matched healthy subjects. The BPs and magnetic resonance imaging-based morphometric measures in iNPH were used for correlation analyses between the magnitude of binding of these in vivo markers and clinical severity of the patients. Analysis of variance showed significant reduction in [11C]raclopride binding in the putamen and nucleus accumbens (P<0.05, corrected for multiple comparison) and unchanged striatal [11C]CFT binding in iNPH. The dorsal putamen [11C]raclopride binding correlated negatively with gait severity (r=0.720, P<0.05), and the nucleus accumbens [11C]raclopride binding correlated positively with emotional recognition score (r=0.727, P<0.05) in the disease group. No significant relationship was observed between BPs and morphometric measures. The current result of the postsynaptic D2 receptor reduction along with preserved presynaptic activity in the nigrostriatal dopaminergic system reflects a pathophysiology of iNPH. Postsynaptic D2 receptor hypoactivity in the dorsal putamen may predict the severity of gait impairment in iNPH.
authors.affiliation: Positron Medical Center, Hamamatsu Medical Center, Hamamatsu, Japan. ouchi@pmc.hmedc.or.jp
authors.forename: Yasuomi
authors.initials: Y
authors.lastname: Ouchi
authors.forename: Teiji
authors.initials: T
authors.lastname: Nakayama
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kanno
authors.forename: Etsuji
authors.initials: E
authors.lastname: Yoshikawa
authors.forename: Tomomi
authors.initials: T
authors.lastname: Shinke
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Torizuka
mesh_terms: D000368:Aged; D002552:Cerebral Ventricles / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives; D003071:Cognition / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D005260:Female; D006801:Humans; D006850:Hydrocephalus, Normal Pressure / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology; D008636:Mesencephalon / Q000473:pathology; D008875:Middle Aged; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000502:physiology*; D009483:Neuropsychological Tests; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D049268:Positron-Emission Tomography; D017729:Presynaptic Terminals / Q000502:physiology*; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D020891:Raclopride / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D013569:Synapses / Q000502:physiology*
chemical_list: D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D020891:Raclopride; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D003042:Cocaine; D004298:Dopamine