Characterization of noradrenaline release in the locus coeruleus of freely moving awake rats by in vivo microdialysis
Characterization of noradrenaline release in the locus coeruleus of freely moving awake rats by in vivo microdialysis
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DOI：
10.1007/s00213-005-2181-y
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发表时间：
2005-07-01
影响因子：
3.4
通讯作者：
Meana, JJ
中科院分区：
文献类型：
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作者：
Fernández-Pastor, B;Mateo, Y;Meana, JJ
基本原理：目的：研究蓝斑（LC）去甲肾上腺素（NA）溢出的神经化学特征（神经冲动依赖性、神经递质合成、囊泡贮存、再摄取、α 2肾上腺素受体介导的调节）。结果：通过局部输注无钙培养基（-42 +/-5%）或钠通道阻滞剂河豚毒素（TTX）（-47 +/-8%），LC中的NA降低，但通过KCl诱导的去极化增加（333 +/-40%）。酪氨酸羟化酶（TH）抑制剂α-甲基-对-酪氨酸（250 mg/kg，i. p.）和囊泡抑制剂利血平（5 mg kg（-1），i. p.）下降NA。因此，细胞外NA在LC满足神经元起源的脉冲流依赖性囊泡胞吐的标准。局部灌注α（2）-肾上腺素受体激动剂可乐定（0.1 - 100 μ M）可降低LC中的NA（E-max=-79 +/-5%），而α（2A）-肾上腺素受体拮抗剂BRL 44408（0.1 - 100 μ M）则观察到相反的作用（E-max= 268 +/-53%）。这表明通过局部α（2A）-肾上腺素受体对NA释放进行紧张性调节。选择性NA再摄取抑制剂LC使LC中NA增加（E-max= 223 +/- 40%），同时使扣带回中NA减少，证实LC中NA对去甲肾上腺素能细胞放电活动和随后的去甲肾上腺素能终末NA释放的调节作用。LC中的NA可以代表局部体树突释放，但也存在来自侧支轴突终末的神经递质释放。
Rationale: The origin and regulation of noradrenaline (NA) in the locus coeruleus (LC) is unknown.Objectives: The neurochemical features of NA overflow ( nerve impulse dependence, neurotransmitter synthesis, vesicle storage, reuptake, alpha(2)-adrenoceptor-mediated regulation) were characterized in the LC.Methods: Brain microdialysis was performed in awake rats. Dialysates were analyzed for NA.Results: NA in the LC decreased via local infusion of Ca2+-free medium (-42 +/- 5%) or the sodium channel blocker tetrodotoxine ( TTX) (- 47 +/- 8%) but increased (333 +/- 40%) via KCl-induced depolarization. The tyrosine hydroxylase (TH) inhibitor alpha-methyl-p-tyrosine (250 mg kg(-1), i.p.) and the vesicle depletory drug reserpine (5 mg kg(-1), i.p.) decreased NA. Therefore, extracellular NA in the LC satisfies the criteria for an impulse flow-dependent vesicular exocytosis of neuronal origin. Local perfusion of the alpha(2)-adrenoceptor agonist clonidine ( 0.1 - 100 mu M) decreased NA(E-max=- 79 +/- 5%) in the LC, whereas the opposite effect (E-max= 268 +/- 53%) was observed with the alpha(2A)-adrenoceptor antagonist BRL44408 ( 0.1 - 100 mu M). This suggests a tonic modulation of NA release through local alpha(2A)-adrenoceptors. The selective NA reuptake inhibitor LC increased NA in the LC (E-max= 223 +/- 40%) and simultaneously decreased NA in the cingulate cortex, confirming the modulation exerted by NA in the LC on firing activity of noradrenergic cells and on the subsequent NA release in noradrenergic terminals.Conclusion: Synaptic processes underlying NA release in the LC are similar to those in noradrenergic terminal areas. NA in the LC could represent local somatodendritic release, but also the presence of neurotransmitter release from collateral axon terminals.