Department of Animal Physiology, Faculty of Science, University of Zagreb, Rooseveltov trg 6, HR-10 000 Zagreb, Croatia.
Behav Brain Res. 2012 Apr 21;230(1):175-81. doi: 10.1016/j.bbr.2012.02.001. Epub 2012 Feb 8.
Serotonin (5-hydroxytryptamine, 5HT) is a biologically active amine that regulates the development of 5HT neurons and target tissues during neurogenesis, while later it assumes the function of a neurotransmitter. Serotonin mediates many essential behaviors common to all mammals, and is held responsible for anxiety-like behavior and cognitive rigidity. Proper serotonin levels, controlled through 5HT synthesis and metabolism, are crucial for normal brain development. In this study we investigated anxiety-like behavior and cognitive flexibility in adult animals after exposing their developing brains to increased 5HT concentrations. Wistar rats were treated subcutaneously from gestational day 12 to post-natal day 21 with the immediate 5HT precursor 5-hydroxytryptophan (5HTP, 25mg/kg), a non-selective MAO inhibitor tranylcypromine (TCP, 2mg/kg), or saline. After reaching adulthood, animals were tested for anxiety-like behavior (exploratory behavior, thigmotactic behavior, social contact, and reaction to stressful stimulus) and cognitive flexibility (ability for reversal learning). Results of the behavioral studies corresponded with our previous neurochemical findings. Treatment with 5HTP, which has induced mild reduction in cortical 5HT concentrations, caused reduction in only one aspect of anxiety-like behavior (increased exploratory activity). Treatment with TCP, which lead to drastic reduction in 5HT concentration/function, resulted in a highly anxiolytic phenotype (reduced thigmotaxis, reaction to stress, and social anxiety) with improved cognitive flexibility. Although further neurochemical, anatomical and gene-expression studies are needed to elucidate the mechanisms underlying the observed behavior, we hope that our results will contribute to the understanding of the role of serotonin in anxiety-like behavior and cognitive rigidity.
血清素（5-羟色胺，5HT）是一种生物活性胺，它在神经发生过程中调节 5HT 神经元和靶组织的发育，而后来则发挥神经递质的作用。血清素介导了所有哺乳动物共有的许多基本行为，并被认为与类似焦虑的行为和认知僵化有关。适当的血清素水平，通过 5HT 的合成和代谢来控制，对正常大脑发育至关重要。在这项研究中，我们研究了在发育中的大脑暴露于增加的 5HT 浓度后，成年动物的类似焦虑的行为和认知灵活性。Wistar 大鼠从妊娠第 12 天到产后第 21 天，每天皮下注射立即 5HT 前体 5-羟色氨酸（5HTP，25mg/kg）、非选择性 MAO 抑制剂反苯环丙胺（TCP，2mg/kg）或生理盐水。成年后，对动物进行类似焦虑的行为（探索行为、触壁行为、社会接触和对应激刺激的反应）和认知灵活性（反转学习能力）测试。行为研究的结果与我们以前的神经化学发现相符。5HTP 处理导致皮质 5HT 浓度轻微降低，仅导致一种类似焦虑的行为减少（探索活动增加）。TCP 处理导致 5HT 浓度/功能急剧降低，导致高度抗焦虑表型（触壁减少、对压力的反应和社交焦虑减少），认知灵活性提高。虽然需要进一步的神经化学、解剖学和基因表达研究来阐明观察到的行为的机制，但我们希望我们的结果将有助于理解血清素在类似焦虑的行为和认知僵化中的作用。
