title: Relation between microPET imaging and rotational behavior in a parkinsonian rat model induced by medial forebrain bundle axotomy.
abstract: The purpose of the current study was to examine the relation between apomorphine (APO) induced rotational behavior and the pre- and post-synaptic dopaminergic function in a parkinsonian rat model induced by medial forebrain bundle (MFB) axotomy. The brains of these rats were unilaterally lesioned by mechanical transection of the nigrostriatal dopamine pathway at the MFB. Behavioral studies were carried out by APO challenge prior to and 1, 3, and 5 weeks after MFB axotomy. MicroPET scans with [(11)C]CFT and [(11)C]raclopride were performed 2 days after the behavioral test. The two PET scans were separated by an interval of 24-48 h. Immunohistochemistry was conducted 4 days after the last PET scan. Our data showed that [(11)C]CFT binding decreased progressively 1, 3, and 5 weeks postlesion, and there was a significant nonlinear correlation between [(11)C]CFT uptake ratio (right/left) and APO induced rotations. In contrast, [(11)C]raclopride binding only increased significantly 3 weeks postlesion, and there was a positive linear correlation between [(11)C]raclopride uptake ratio (right/left) and APO induced rotations. Postmortem immunohistochemical studies confirmed the loss of both striatal dopamine fibers and nigral neurons on the lesioned side. These findings not only demonstrate the relation between APO induced rotational behavior and the pre- and post-synaptic dopamine function but also indicate the utility and validity of in vivo PET imaging in understanding disease mechanisms and progression, which should in turn lead to development of new therapies.
authors.affiliation: Department of Physiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, PR China.
authors.forename: Limin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, PR China.
authors.forename: Wenzhong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, PR China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
authors.forename: Xibin
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Neurobiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, PR China. Electronic address: xmwang@ccmu.edu.cn.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D019771:Axotomy; D003042:Cocaine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D018765:Dopamine Uptake Inhibitors / Q000493:pharmacokinetics; D007839:Functional Laterality; D008297:Male; D008474:Medial Forebrain Bundle / Q000293:injuries*; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000209:etiology*; D020891:Raclopride / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D013239:Stereotyped Behavior / Q000502:physiology*; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D020891:Raclopride; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D014446:Tyrosine 3-Monooxygenase; D003042:Cocaine; D001058:Apomorphine
keywords: Apomorphine; Parkinsonian rat model; Rotational behavior; [(11)C]CFT; [(11)C]raclopride