Chronic citalopram administration causes a sustained suppression of serotonin synthesis in the mouse forebrain.
Chronic citalopram administration causes a sustained suppression of serotonin synthesis in the mouse forebrain.
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DOI：
10.1371/journal.pone.0006797
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发表时间：
2009-08-27
期刊：
影响因子：
3.7
通讯作者：
Tecott LH
中科院分区：
文献类型：
--
作者：
Honig G;Jongsma ME;van der Hart MC;Tecott LH
5-羟色胺（5-HT）是一种神经递质，在调节神经行为过程中起着重要作用，特别是在调节人类的神经行为过程中。通过选择性抑制5 -羟色胺再摄取（SSRIs）来增强5 -羟色胺能神经传递的药物被广泛用于精神疾病的治疗。虽然调节5-羟色胺合成可能是SSRI疗效的一个因素，但长期服用SSRI对5-羟色胺合成的影响尚不清楚。在这里，我们描述了长期服用SSRI西酞普兰（CIT）对小鼠前脑5-羟色胺合成和含量的影响。成年雄性C57BL/6J小鼠经渗透微型泵连续给予西酞普兰2 d、14 d和28 d。血浆西酞普兰水平在临床范围内。用脱羧酶抑制法评价5-羟色胺的合成。西酞普兰在所有时间点引起5-羟色胺合成的抑制。CIT处理也导致前脑5-HIAA含量降低。慢性CIT治疗后，前脑5-HT储存对急性脱羧酶抑制的消耗效应更敏感。综上所述，这些结果表明，长期服用西酞普兰会导致小鼠前脑血清素合成的持续抑制。此外，我们的研究结果表明，慢性5-羟色胺再摄取抑制使5-羟色胺脑储存对5-羟色胺合成的改变更敏感。这些结果表明，在开发新的抗抑郁药物策略的努力中，5-羟色胺合成的调节值得考虑。
Serotonin (5-HT) is a neurotransmitter with important roles in the regulation of neurobehavioral processes, particularly those regulating affect in humans. Drugs that potentiate serotonergic neurotransmission by selectively inhibiting the reuptake of serotonin (SSRIs) are widely used for the treatment of psychiatric disorders. Although the regulation of serotonin synthesis may be an factor in SSRI efficacy, the effect of chronic SSRI administration on 5-HT synthesis is not well understood. Here, we describe effects of chronic administration of the SSRI citalopram (CIT) on 5-HT synthesis and content in the mouse forebrain. Citalopram was administered continuously to adult male C57BL/6J mice via osmotic minipump for 2 days, 14 days or 28 days. Plasma citalopram levels were found to be within the clinical range. 5-HT synthesis was assessed using the decarboxylase inhibition method. Citalopram administration caused a suppression of 5-HT synthesis at all time points. CIT treatment also caused a reduction in forebrain 5-HIAA content. Following chronic CIT treatment, forebrain 5-HT stores were more sensitive to the depleting effects of acute decarboxylase inhibition. Taken together, these results demonstrate that chronic citalopram administration causes a sustained suppression of serotonin synthesis in the mouse forebrain. Furthermore, our results indicate that chronic 5-HT reuptake inhibition renders 5-HT brain stores more sensitive to alterations in serotonin synthesis. These results suggest that the regulation of 5-HT synthesis warrants consideration in efforts to develop novel antidepressant strategies.
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影响因子：
3.3
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