title: Interpreting DTBZ binding data in rodent: Inherent variability and compensation.
abstract: [11C]-dihydrotetrabenazine (DTBZ) Positron Emission Tomography was used to evaluate the vesicular monoamine transporter type 2 as an index of dopaminergic function in the striatum of adult Sprague-Dawley rats obtained from two different animal sources (Charles River Laboratories [CR] or UBC's Animal Care Centre [ACC]) and later submitted to two different unilateral lesions of the nigro-striatal pathway. The results showed a significant difference in the striatal binding potential (BP(ND)) at baseline (before lesioning) between the CR and ACC groups providing evidence that the origin of the animals, possibly due to differences in early environmental factors or breeding conditions associated with different animal vendors plays a role in the development of the adult dopaminergic system. Further, in both animal models, an increase in DTBZ BP(ND) was observed, after unilateral intervention, in the striatum contralateral to the lesion, likely reflecting compensatory effects. Based on these findings, we conclude that in unilateral models, the unlesioned side/hemisphere may not be an appropriate control and that care should be taken to control for the origin of the animals in any given study, especially in longitudinal and replication studies.
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Miguel
authors.initials: M
authors.lastname: Mejias
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.|Department of Nuclear Medicine, Da Lian Medical University Affiliated Hospital No 2, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.|Department of Psychiatry, University of Vermont, Burlington, Vermont.
authors.forename: Scott
authors.initials: S
authors.lastname: Mackey
authors.affiliation: Department of Physics and Astronomy, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Katie
authors.initials: K
authors.lastname: Dinelle
authors.affiliation: Department of Physics and Astronomy, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Vesna
authors.initials: V
authors.lastname: Sossi
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Doris J
authors.initials: DJ
authors.lastname: Doudet
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D003627:Data Interpretation, Statistical; D049268:Positron-Emission Tomography / Q000379:methods / Q000592:standards; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*
chemical_list: C575320:(11C)-(+)-alpha-dihydrotetrabenazine; D019275:Radiopharmaceuticals; C493454:Slc18a2 protein, rat; D050493:Vesicular Monoamine Transport Proteins; D013747:Tetrabenazine
keywords: 6-OHDA; VMAT2; compensatory changes; dopamine; lactacystin; striatum