RRC ID 158
著者 Inaji M, Okauchi T, Ando K, Maeda J, Nagai Y, Yoshizaki T, Okano H, Nariai T, Ohno K, Obayashi S, Higuchi M, Suhara T.
タイトル Correlation between quantitative imaging and behavior in unilaterally 6-OHDA-lesioned rats.
ジャーナル Brain Res
Abstract We evaluated correlation between neurochemical and functional alterations of the nigrostriatal dopaminergic system in rat brains lesioned with 6-hydroxydopamine (6-OHDA), that model hemi-Parkinson's disease (PD), by using three different quantitative in vivo and in vitro methods. Rats unilaterally lesioned with different doses of 6-OHDA underwent two types of in vivo experiments: (1) a rotational behavioral study with methamphetamine (MAP) or apomorphine (APO); and (2) a positron emission tomography (PET) study with [11C]PE2I (radioligand for dopamine transporters) or [11C]raclopride (radioligand for dopamine D2 receptors). An in vitro autoradiographic study with the same radioligands was also conducted. The number of rotations after the MAP or APO injection increased with increased doses of 6-OHDA. The in vitro and in vivo binding of [11C]PE2I dose-dependently decreased in response to the 6-OHDA injections, while that of [11C]raclopride dose-dependently increased. There was a significant negative hyperbolic correlation between the number of rotations after MAP injection and the binding of [11C]PE2I. In contrast, there was a significant positive linear correlation between the number of rotations after APO injections and the binding of [11C]raclopride. These results robustly reveal a molecular pharmacological basis of parkinsonian symptoms in animal models of PD, and indicate the utility and validity of in vivo PET measurements in assessing pre- and post-synaptic dopaminergic functions.
巻・号 1064(1-2)
ページ 136-45
公開日 2005-12-7
DOI 10.1016/j.brainres.2005.09.055
PII S0006-8993(05)01306-5
PMID 16298352
MeSH Animals Apomorphine / pharmacology Autoradiography Behavior, Animal / drug effects Behavior, Animal / physiology* Dopamine / metabolism* Dopamine Agents / administration & dosage Dopamine Plasma Membrane Transport Proteins / drug effects Dopamine Plasma Membrane Transport Proteins / metabolism Dose-Response Relationship, Drug Functional Laterality* Male Methamphetamine / pharmacology Movement* Neostriatum / diagnostic imaging Neostriatum / drug effects Neostriatum / metabolism Neurons / drug effects Neurons / pathology Oxidopamine / administration & dosage Parkinsonian Disorders / chemically induced Parkinsonian Disorders / diagnostic imaging Parkinsonian Disorders / metabolism* Positron-Emission Tomography Rats Rats, Sprague-Dawley Receptors, Dopamine D2 / drug effects Receptors, Dopamine D2 / metabolism
IF 2.733
引用数 41
WOS 分野 NEUROSCIENCES
リソース情報
ラット