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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Acute effects of combining citalopram and pindolol on regional brain serotonin synthesis in sham operated and olfactory bulbectomized rats.
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Acute effects of combining citalopram and pindolol on regional brain serotonin synthesis in sham operated and olfactory bulbectomized rats.

机译：西酞普兰和品多洛尔组合对假手术和嗅球切除大鼠的局部脑5-羟色胺合成的急性影响。

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The olfactory bulbectomized (OBX) rat is considered to be a good model of the pathology of human depression and also of the functional actions of antidepressant drug therapy. It has been proposed that antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) can be accelerated by blocking 5-HT(1A/B) autoreceptors with pindolol. The underlying mechanism is thought to involve acute unrestricting of 5-HT release and, consequently, relatively enhanced 5-HT turnover throughout the forebrain serotonergic networks. The effect of this combination on 5-HT turnover in sham operated or OBX rats can be assessed at the level of 5-HT synthesis, a very important presynaptic step in serotonergic neurotransmission, using the alpha-[(14)C]methyl-l-tryptophan autoradiography method. In sham rats, acute citalopram (20mg/kg) treatment increased synthesis at almost all serotonergic terminal regions but slightly decreased synthesis at serotonergic cell body regions (i.e. dorsal and median (not significant) raphe; approximately 16%). Combining pindolol (10mg/kg) with citalopram further increased synthesis at many regions in sham rats (relative to treatment with only citalopram). In OBX rats, citalopram decreased synthesis at a few terminal regions and greatly decreased synthesis at the dorsal and median raphe ( approximately 45%; relative to OBX rats treated with saline). Combining pindolol with citalopram greatly increased synthesis at almost all regions in OBX rats (relative to treatment with only citalopram). These results suggest that acute citalopram effects result in elevated terminal 5-HT synthesis, but these effects are restrained by 5-HT(1A/B) autoreceptor feedback to different degrees in sham and OBX rats. Moreover, 5-HT(1A/B) autoreceptor feedback is stronger in OBX rats and may underlie the delay of SSRI effects in OBX rats and, correspondingly, in human depression. Pindolol acceleration and augmentation of SSRI antidepressant therapy for human depression may be mediated by attenuation of 5-HT(1A/B) autoreceptor feedback, permitting unhindered SSRI effects on serotonergic terminals.
机译：嗅球切除术（OBX）大鼠被认为是人类抑郁症以及抗抑郁药物治疗功能作用的良好模型。有人提出，可以通过用潘多洛尔阻断5-HT（1A / B）自体受体来加速选择性5-羟色胺再摄取抑制剂（SSRIs）的抗抑郁作用。据认为，潜在的机制涉及5-HT释放的急性不受限制，因此，整个前脑5-羟色胺能神经网络中5-HT的转换相对增强。该组合对假手术或OBX大鼠5-HT转换的影响可以使用α-[（14）C]甲基-1在5-HT合成水平进行评估，5-HT合成是血清素神经传递中非常重要的突触前步骤。 -色氨酸放射自显影方法。在假大鼠中，急性西酞普兰（20mg / kg）处理几乎在所有血清素能末梢区域增加了合成，但在血清素能细胞体区域（即背侧和中位数（无显着性）缝隙;约16％）上的合成略有下降。将伪吲哚洛尔（10mg / kg）与西酞普兰组合使用可进一步提高假手术大鼠许多部位的合成（相对于仅使用西酞普兰治疗）。在OBX大鼠中，西酞普兰在少数末端区域降低了合成，而在背侧和正中线则大大降低了合成（相对于用盐水处理的OBX大鼠，约为45％）。将匹多洛尔与西酞普兰组合使用可大大提高OBX大鼠几乎所有区域的合成（相对于仅使用西酞普兰治疗）。这些结果表明急性西酞普兰的作用导致增加5-HT合成终端，但这些影响受到假和OBX大鼠5-HT（1A / B）自体受体不同程度的抑制。此外，在OBX大鼠中5-HT（1A / B）自身受体反馈较强，并且可能是OBX大鼠以及相应地在人类抑郁症中SSRI效应延迟的基础。品多洛尔对人抑郁症的SSRI抗抑郁药治疗的加速和增强可能通过5-HT（1A / B）自体受体反馈的减弱来介导，从而使SSRI对血清素能终末受体的作用不受阻碍。

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