Olivier J D A, Jans L A W, Korte-Bouws G A H, Korte S M, Deen P M T, Cools A R, Ellenbroek B A, Blokland A
Department of Cognitive Neuroscience: Psychoneuropharmacology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Psychopharmacology (Berl). 2008 Oct;200(2):243-54. doi: 10.1007/s00213-008-1201-0. Epub 2008 Jun 10.
Acute tryptophan depletion (ATD) transiently lowers central serotonin levels and can induce depressive mood states and cognitive defects. Previous studies have shown that ATD impairs object recognition in rats.
As individual differences exist in central serotonin neurotransmission, the impact of ATD may vary accordingly. In this experiment, we investigated the hypothesis that male serotonin transporter knockout (SERT(-/-)), rats marked by a lower SERT function, are more vulnerable to the effects of ATD in an object recognition task than male wildtype (SERT(+/+)) and heterozygous (SERT(+/-)) rats.
Twelve male SERT(+/+), SERT(+/-), and SERT(-/-) rats were treated with standard dose and low-dose ATD using a gelatine-based protein-carbohydrate mixture lacking tryptophan. In the control treatment, L: -tryptophan was added to the mixture. Four hours after treatment, the rats were subjected to the object recognition task. In addition, the effects of ATD on plasma amino acid concentrations were measured, and concentrations of 5-HT and 5-HIAA were measured in the frontal cortex and hippocampus of these rats.
Plasma TRP levels and central 5-HT and 5-HIAA levels were decreased in all genotypes after ATD, but effects were stronger in SERT(-/-) rats. The standard dose of ATD impaired object recognition in all genotypes. SERT(-/-) and SERT(+/-) rats were more vulnerable to low dose of ATD in the object recognition task compared to SERT(+/+) rats.
These results indicate a greater sensitivity to ATD in SERT(-/-) and SERT(+/-) rats, which may be related to stronger central depletion effects in these rats.
急性色氨酸耗竭（ATD）会使中枢5-羟色胺水平暂时降低，并可诱发抑郁情绪状态和认知缺陷。先前的研究表明，ATD会损害大鼠的物体识别能力。
由于中枢5-羟色胺神经传递存在个体差异，ATD的影响可能也会相应有所不同。在本实验中，我们研究了这样一个假设：即雄性血清素转运体基因敲除（SERT(-/-)）大鼠（其特征为SERT功能较低）在物体识别任务中比雄性野生型（SERT(+/+)）和杂合子（SERT(+/-)）大鼠更容易受到ATD的影响。
使用不含色氨酸的明胶基蛋白质-碳水化合物混合物，对12只雄性SERT(+/+)、SERT(+/-)和SERT(-/-)大鼠进行标准剂量和低剂量的ATD处理。在对照处理中，向混合物中添加L-色氨酸。处理后4小时，让大鼠进行物体识别任务。此外，还测量了ATD对血浆氨基酸浓度的影响，并测定了这些大鼠额叶皮质和海马体中5-羟色胺（5-HT）和5-羟吲哚乙酸（5-HIAA）的浓度。
ATD处理后，所有基因型大鼠的血浆色氨酸（TRP）水平以及中枢5-HT和5-HIAA水平均降低，但SERT(-/-)大鼠的影响更强。标准剂量的ATD损害了所有基因型大鼠的物体识别能力。与SERT(+/+)大鼠相比，SERT(-/-)和SERT(+/-)大鼠在物体识别任务中更容易受到低剂量ATD的影响。
这些结果表明，SERT(-/-)和SERT(+/-)大鼠对ATD更为敏感，这可能与这些大鼠更强的中枢耗竭效应有关。
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