Addendum: Paroxetine-induced increase in activity of locus coeruleus neurons in adolescent rats: implication of a countertherapeutic effect of an antidepressant.
Addendum: Paroxetine-induced increase in activity of locus coeruleus neurons in adolescent rats: implication of a countertherapeutic effect of an antidepressant.
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附录：帕罗西汀诱导的青少年大鼠蓝斑神经元活性增加：抗抑郁药的反治疗作用的含义。
DOI：
10.1038/npp.2010.54
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Weiss,JayM
中科院分区：
文献类型：
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作者：
West,CharlesHK;Ritchie,JamesC;Weiss,JayM
在本期杂志中，我们报道了帕罗西汀（PAR），当给予幼年大鼠（青春期）中等剂量时，在给药过程的早期会增加蓝斑（LC）神经元的电生理活动（West et al, 2010）。这种对 LC 活性的影响与抗抑郁 (AD) 药物给药治疗方案（即长期给药 AD 药物）产生的 LC 活性通常降低相反。相比之下，在用 PAR 治疗的成年大鼠中观察到的唯一影响是 LC 活性通常降低，在所检查的任何剂量或治疗持续时间下均未观察到 LC 活性增加。因此，幼年动物治疗早期对 PAR 的 LC 反应表明存在反治疗反应，可能与抑郁症状的增加有关，特别是自杀意念，据说在一些青少年接受 PAR 和其他 SSRIs 治疗的早期会出现这种情况。在提交上述文章后，我们收集了测试另外两种 AD 药物的数据，其中一种药物也与自杀风险增加有关，即双重 5-羟色胺 - NE 再摄取抑制剂文拉法辛 (VEN) 和与此类风险关系最小的 AD，三环地昔帕明 (DMI)，其阻断能力很小
In this issue of the journal, we report that paroxetine (PAR), when given to young rats (adolescent age) in moderate doses, produced an increase in electrophysiological activity of locus coeruleus (LC) neurons early in the course of drug administration (West et al, 2010). This effect on LC activity is opposite to the usual decrease in LC activity produced by therapeutic regimens of antidepressant (AD) drug administration (ie, chronic administration of AD drugs). In contrast, the only effects seen in mature adult rats treated with PAR were the usual decreases in LC activity, with no increases seen at any dose or duration of treatment examined. Therefore, the LC response to PAR early in treatment of young animals suggests a countertherapeutic reaction that may relate to an increase in depressive symptomatology, and suicidal ideation in particular, said to occur in some adolescents early in treatment with PAR and other SSRIs.Following submission of the article described above, we collected data from testing two additional AD drugs, one also associated with the risk of increased suicidality, the dual serotonin–NE reuptake inhibitor venlafaxine (VEN), and an AD minimally associated with such risk, the tricyclic desipramine (DMI), which has little capacity to block