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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Sulpiride, but not SCH23390, modifies cocaine-induced conditioned place preference and expression of tyrosine hydroxylase and elongation factor 1α in zebrafish
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Sulpiride, but not SCH23390, modifies cocaine-induced conditioned place preference and expression of tyrosine hydroxylase and elongation factor 1α in zebrafish

机译：舒必利，但不是SCH23390，可改变可卡因诱导的条件性位置偏爱以及酪氨酸羟化酶和延伸因子1α在斑马鱼中的表达

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Finding genetic polymorphisms and mutations linked to addictive behavior can provide important targets for pharmaceutical and therapeutic interventions. Forward genetic approaches in model organisms such as zebrafish provide a potentially powerful avenue for finding new target genes. In order to validate this use of zebrafish, the molecular nature of its reward system must be characterized. We have previously reported the use of cocaine-induced conditioned place preference (CPP) as a reliable method for screening mutagenized fish for defects in the reward pathway. Here we test if CPP in zebrafish involves the dopaminergic system by co-treating fish with cocaine and dopaminergic antagonists. Sulpiride, a potent D2 receptor (DR2) antagonist, blocked cocaine-induced CPP, while the D1 receptor (DR1) antagonist SCH23390 had no effect. Acute cocaine exposure also induced a rise in the expression of tyrosine hydroxylase (TH), an important enzyme in dopamine synthesis, and a significant decrease in the expression of elongation factor 1α (EF1α), a housekeeping gene that regulates protein synthesis. Cocaine selectively increased the ratio of TH/EF1α in the telencephalon, but not in other brain regions. The cocaine-induced change in TH/EF1α was blocked by co-treatment with sulpiride, but not SCH23390, correlating closely with the action of these drugs on the CPP behavioral response. Immunohistochemical analysis revealed that the drop in EF1α was selective for the dorsal nucleus of the ventral telencephalic area (Vd), a region believed to be the teleost equivalent of the striatum. Examination of TH mRNA and EF1α transcripts suggests that regulation of expression is post-transcriptional, but this requires further examination. These results highlight important similarities and differences between zebrafish and more traditional mammalian model organisms.
机译：发现与成瘾行为相关的遗传多态性和突变可以为药物和治疗干预提供重要目标。模型生物（例如斑马鱼）中的正向遗传方法为寻找新的靶基因提供了潜在的强大途径。为了验证斑马鱼的这种使用，必须表征其奖励系统的分子性质。我们以前曾报道过可卡因诱导的条件性位置偏爱（CPP）作为筛选诱变鱼中奖励途径缺陷的可靠方法。在这里，我们通过将鱼与可卡因和多巴胺能拮抗剂共同处理来测试斑马鱼中的CPP是否涉及多巴胺能系统。舒必利是一种有效的D2受体（DR2）拮抗剂，阻断了可卡因诱导的CPP，而D1受体（DR1）拮抗剂SCH23390没有作用。急性可卡因暴露还引起酪氨酸羟化酶（TH）的表达增加，酪氨酸羟化酶是多巴胺合成中的一种重要酶，而延伸因子1α（EF1α）的表达则显着下降，这是调节蛋白质合成的管家基因。可卡因选择性地增加了末梢脑TH /EF1α的比率，但在其他脑部区域却没有。可卡因诱导的TH /EF1α变化被舒必利（但不与SCH23390）共同治疗所阻断，与这些药物对CPP行为反应的作用密切相关。免疫组织化学分析显示，EF1α的下降对腹侧脑末梢区域（Vd）的背核具有选择性，该区域被认为是纹状体的硬骨等效区域。检查TH mRNA和EF1α转录本表明表达调控是转录后的，但这需要进一步检查。这些结果突出了斑马鱼与更传统的哺乳动物模型生物之间的重要异同。

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