Extracellular dopamine, acetylcholine, and activation of dopamine D1 and D2 receptors after selective breeding for cocaine self-administration in rats.
Extracellular dopamine, acetylcholine, and activation of dopamine D1 and D2 receptors after selective breeding for cocaine self-administration in rats.
复制标题
大鼠选择性繁殖可卡因自我给药后的细胞外多巴胺、乙酰胆碱以及多巴胺 D1 和 D2 受体的激活。
DOI：
10.1007/s00213-017-4640-7
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发表时间：
2017
影响因子：
3.4
通讯作者：
Grasing,Kenneth
中科院分区：
文献类型：
--
作者：
Xu,Haiyang;Das,Sasmita;Sturgill,Marc;Hodgkinson,Colin;Yuan,Qiaoping;Goldman,David;Grasing,Kenneth
低自我给药（LS）/Kgras（LS）和高自我给药（HS）/Kgras（HS）大鼠系分别通过选择性繁殖低和高静脉内可卡因自我给药，从一个普通远交Wistar股票（Crl：WI）。这一特点一直保持稳定后，13代breeding. ESTA本研究的目的是比较可卡因的偏好，神经递质的释放，多巴胺受体激活LS和HS rats.MethodsLevels的多巴胺，乙酰胆碱，可卡因测定在HS和LS大鼠的延髓核（NA）壳串联质谱的微透析。可卡因诱导的自发活动和条件性位置偏爱LS和HS rats.ResultsHS大鼠之间进行了比较显示更大的条件性位置偏爱评分相比，LS和基础细胞外多巴胺和乙酰胆碱浓度降低。然而，神经递质释放的模式没有不同的菌株。低剂量的可卡因增加LS大鼠的自发活动，但不是在HS动物，而高剂量的可卡因增加活动只在HS大鼠。任何剂量的可卡因增加免疫反应c-Fos在NA壳的两个菌株，与HS大鼠中观察到更大的海拔。活化鉴定细胞表达c-Fos和多巴胺受体一般是更大的HS株，与D1和D2多巴胺receptor.ConclusionsDiminished水平的多巴胺和乙酰胆碱在NA壳，增强可卡因诱导的表达D1和D2受体，与可卡因在HS大鼠中的更大奖赏效应和可卡因诱导的运动活动的改变的剂量-效应关系相关。
RationaleThe low self-administration (LS)/Kgras (LS) and high self-administration (HS)/Kgras (HS) rat lines were generated by selective breeding for low- and high-intravenous cocaine self-administration, respectively, from a common outbred Wistar stock (Crl:WI). This trait has remained stable after 13 generations of breeding.ObjectiveThe objective of the present study is to compare cocaine preference, neurotransmitter release, and dopamine receptor activation in LS and HS rats.MethodsLevels of dopamine, acetylcholine, and cocaine were measured in the nucleus accumbens (NA) shell of HS and LS rats by tandem mass spectrometry of microdialysates. Cocaine-induced locomotor activity and conditioned-place preference were compared between LS and HS rats.ResultsHS rats displayed greater conditioned-place preference scores compared to LS and reduced basal extracellular concentrations of dopamine and acetylcholine. However, patterns of neurotransmitter release did not differ between strains. Low-dose cocaine increased locomotor activity in LS rats, but not in HS animals, while high-dose cocaine augmented activity only in HS rats. Either dose of cocaine increased immunoreactivity for c-Fos in the NA shell of both strains, with greater elevations observed in HS rats. Activation identified by cells expressing both c-Fos and dopamine receptors was generally greater in the HS strain, with a similar pattern for both D1 and D2 dopamine receptors.ConclusionsDiminished levels of dopamine and acetylcholine in the NA shell, with enhanced cocaine-induced expression of D1 and D2 receptors, are associated with greater rewarding effects of cocaine in HS rats and an altered dose-effect relationship for cocaine-induced locomotor activity.