Serotoninergic modulation of exogenous L-DOPA-derived dopamine release in rats with unilateral 6-OHDA lesions revealed with microPET imaging

摘要: Serotoninergic modulation of exogenous L-DOPA-derived dopamine release in rats with unilateral 6OHDA lesions revealed microPET imaging   Adjmal Nahimi 1,2 , Mette HA¸lzermann Simonsen 2  Kim Vang, Steen Jakobsen Anne Landau Arne MA¸ller Gregers Wegener 3 Albert Gjedde and Doris Doudet 1 Centre Functionally Integrative Neuroscience, Aarhus University Denmark PET-Center, Hospitals Center Psychiatric Research, Hospital, Introduction: L-DOPA induced dyskinesias, a severe complication parkinsonian therapy, occur response to administration therapeutic doses are modulated by rapid changes extracellular DA. Recently, the use 5-HT agonists antagonists as potential adjuncts modulate DA without loss benefits, has started be actively investigated. We used raclopride, tracer D /D receptors which can surrogate marker DA-release evaluate in-vivo effect 8-OH-DPAT, agonist, on 6-OHDA lesioned rats. Methods: Rats (N=6) nigro-striatal pathways received [ 11 C] raclopride micro-PET scans over several days conditions. A baseline scan was followed two pharmacological challenges either L-DOPA+Benzeraside (50/25 mg/kg S.C.) or L-DOPA+Benzeraside+8-OH-DPAT (0,6mg/kg/S.C.) administered 30-45 minutes prior injection. Results:  There little change binding unlesioned striatum challenge compared baseline. In striata, there decrease after administration, agreement increased Concurrent 8-OH-DPAT reduced alone. Conclusion: This study 1) demonstrated feasibility using studies assess 2) supported continued evaluation drugs that serotonin system possible agents PD dyskinesia. Â