Behavioral sensitization to quinpirole is not associated with increased nucleus accumbens dopamine overflow
Behavioral sensitization to quinpirole is not associated with increased nucleus accumbens dopamine overflow
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DOI：
10.1016/s0028-3908(02)00328-3
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发表时间：
2003-01-01
影响因子：
4.7
通讯作者：
Vezina, P
中科院分区：
文献类型：
--
作者：
Koeltzow, TE;Austin, JD;Vezina, P
本研究评估了反复给予DA d2样受体激动剂喹匹罗后，细胞外伏隔核（NAc）多巴胺（DA）浓度与致敏运动激活之间的关系。在第一次（急性）和第十次（重复）注射喹匹罗（0.5 mg/kg s.c，每隔一天）后，同时收集运动活动测量和伏隔核微透析样本。结果表明，急性使用喹匹罗可引起运动激活，重复使用喹匹罗可引起运动致敏。急性喹匹罗显著降低了NAc细胞外DA浓度及DA代谢物二羟基苯乙酸（DOPAC）和高香草酸（HVA）的检测。重复使用喹匹罗后，基础NAc - DA水平降低，而基础DOPAC水平升高。然而，在重复治疗后，喹匹罗刺激引起DA、DOPAC和HVA的显著降低。此外，虽然急性喹匹罗不影响血清素代谢物5-羟基吲哚乙酸（5-HIAA）的NAc水平，但在重复治疗后，喹匹罗刺激会显著增加5-HIAA水平。综上所述，这些数据表明功能性DA自身受体亚敏感并不是表达对喹匹罗行为致敏的必要条件。相反，对喹匹罗的行为致敏似乎主要是突触后对DA释放的神经适应的结果。(C) 2002 Elsevier Science Ltd.版权所有。
This study assessed the relationship between extracellular nucleus accumbens (NAc) dopamine (DA) concentrations and sensitized locomotor activation following repeated administration of the DA D2-like receptor agonist quinpirole. Locomotor activity measures and nucleus accumbens microdialysis samples were collected concurrently in response to the first (acute) and tenth (repeated) quinpirole injection (0.5 mg/kg s.c., every other day). Results indicate that acute quinpirole produced locomotor activation and that repeated quinpirole resulted in locomotor sensitization. Acute quinpirole significantly decreased the detection of extracellular concentrations of DA and the DA metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the NAc. Following repeated quinpirole, basal NAc DA levels were decreased, whereas basal DOPAC levels were increased. Nevertheless, quinpirole challenge elicited a significant decrease in DA, DOPAC and HVA following repeated treatment. In addition, although acute quinpirole did not affect NAc levels of the serotonin metabolite 5-hydroxyindolacetic acid (5-HIAA), quinpirole challenge produced a significant increase in 5-HIAA levels following repeated treatment. Taken together, these data indicate that functional DA autoreceptor subsensitivity is not a necessary condition for the expression of behavioral sensitization to quinpirole. Instead, it appears that behavioral sensitization to quinpirole occurs predominantly as a consequence of neuroadaptations that are post-synaptic to DA release. (C) 2002 Elsevier Science Ltd. All rights reserved.