title: DAT versus D2 receptor binding in the rat striatum: l-DOPA-induced motor activity is better predicted by reuptake than release of dopamine.
abstract: The reuptake and release of dopamine (DA) can be estimated using in vivo imaging methods by assessing the competition between endogenous DA and an administered exogenous DA transporter (DAT) and D2 receptor (D2 R) radioligand, respectively. The aim of this study was to investigate the comparative roles of DA release vs DA reuptake in the rat striatum with small animal SPECT in relation to l-DOPA-induced behaviors. DAT and D2 R binding, together with behavioral measures, were obtained in 99 rats in response to treatment with either 5 or 10 mg/kg l-DOPA or vehicle. The behavioral parameters included the distance travelled, and durations and frequencies of ambulation, sitting, rearing, head-shoulder motility, and grooming. Data were subjected to a cluster analysis and to a multivariate principal component analysis. The highest DAT binding (i.e., the lowest DA reuptake) was associated with the highest, and the lowest DAT binding (i.e., the highest DA reuptake) was associated with the lowest motor/exploratory activity. The highest and the lowest D2 R binding (i.e., the lowest and the highest DA release, respectively) were merely associated with the second highest and second lowest levels of motor/exploratory activity. These findings indicate that changes in DA reuptake in response to fluctuating DA levels offer a better prediction of motor activity than the release of DA into the synaptic cleft. This dissociation, as reflected by in vivo DAT and D2 R binding data, may be accounted for by the regulatory sensitization meachnisms that occur at D2 R binding sites in response to altered levels of DA. Synapse 70:369-377, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Clinic of Nuclear Medicine, University Hospital Düsseldorf, D-40225, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Nikolaus
authors.affiliation: Clinic of Nuclear Medicine, University Hospital Düsseldorf, D-40225, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Beu
authors.affiliation: Center for Behavioural Neuroscience, Heinrich-Heine University, Düsseldorf, D-40225, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Angelica De Souza Silva
authors.affiliation: Center for Behavioural Neuroscience, Heinrich-Heine University, Düsseldorf, D-40225, Germany.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Huston
authors.affiliation: Clinic of Nuclear Medicine, University Hospital Düsseldorf, D-40225, Germany.
authors.forename: Hubertus
authors.initials: H
authors.lastname: Hautzel
authors.affiliation: Clinic of Nuclear Medicine, University Hospital Düsseldorf, D-40225, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Antke
authors.affiliation: Clinic of Nuclear Medicine, University Hospital Düsseldorf, D-40225, Germany.
authors.forename: Hans-Wilhelm
authors.initials: HW
authors.lastname: Müller
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D004705:Endocytosis; D005089:Exocytosis; D005106:Exploratory Behavior; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D009043:Motor Activity; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism
chemical_list: D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D017448:Receptors, Dopamine D2; D007980:Levodopa; D004298:Dopamine
keywords: L-DOPA methylester, small animal SPECT; [123I]FP-CIT; [123I]IBZM