Antidepressant drugs with differing pharmacological actions decrease activity of locus coeruleus neurons.
Antidepressant drugs with differing pharmacological actions decrease activity of locus coeruleus neurons.
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DOI：
10.1017/s1461145708009474
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发表时间：
2009-06
期刊：
影响因子：
--
通讯作者：
Weiss JM
中科院分区：
文献类型：
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作者：
West CH;Ritchie JC;Boss-Williams KA;Weiss JM
以往的研究表明，所有有效的抗抑郁药（AD）都能降低蓝斑（LC）神经元的活性。然而，在这些研究中，关于血液中药物水平的数据很少，而现有的数据表明血液中药物水平可能非常高。为了评估在治疗相关的血液水平上选择性阻断去甲肾上腺素或血清素再摄取的药物是否会导致LC活性降低，我们测量了在不同剂量和血液水平下，慢性给药地西帕明、帕罗西汀和艾司西酞普兰对LC活性的影响。此外，研究了一系列剂量的米氮平的影响；在米氮平阻断α2肾上腺素能受体的情况下，可能会增加而不是降低LC活性。最后，为了开始评估LC对ad的反应是否对这些药物具有特异性，我们测量了四种非ad药物（单剂量）的作用。通过渗透微型泵给药14 d。然后在异氟醚麻醉下，在药物治疗的最后一天进行LC活性的电生理记录（评估自发放电率和感觉诱发的“爆发”放电）。记录结束时还测量了血液中药物的含量。所有测试的AD药物都降低了LC自发和感觉诱发的“爆发”放电，并且在药物的大范围血液水平中都观察到这一点。非ad药物不降低LC活性。这项研究的结果继续支持所有有效的AD药物降低LC活性的可能性。
Previous studies suggest that all effective antidepressant (AD) drugs decrease activity of locus coeruleus (LC) neurons. However, little data exist regarding blood levels of drug in these studies, and what data do exist suggest blood levels might have been very high. To assess whether decreased LC activity is produced by drugs that selectively block reuptake for either norepinephrine or serotonin at therapeutically relevant blood levels, effects of chronic administration of desipramine, paroxetine, and escitalopram on LC activity were measured across a range of doses and blood levels of drug. Further, effects of a range of doses of mirtazapine were examined; in that mirtazapine blocks α2 adrenergic receptors, it might be anticipated to increase rather than decrease LC activity. Finally, to begin to assess whether the response of LC to ADs was specific to these drugs, effects of four non-AD drugs (single dose) were measured. Drugs were administered via osmotic minipump for 14 d. Electrophysiological recording of LC activity (assessment of both spontaneous firing rate and sensory-evoked ‘burst’ firing) then took place under isoflurane anaesthesia on the last day of drug treatment. The blood level of drugs present at the end of the recording session was also measured. All AD drugs tested decreased LC spontaneous and sensory-evoked ‘burst’ firing, and this was observed across a wide range of blood levels for the drugs. Non-AD drugs did not decrease LC activity. The findings of this investigation continue to support the possibility that all effective AD drugs decrease LC activity.