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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 >Both acute and subchronic treatments with pindolol, a 5-HT1A and β1 and β2 adrenoceptor antagonist, elevate regional serotonin synthesis in the rat brain: An autoradiographic study
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Both acute and subchronic treatments with pindolol, a 5-HT1A and β1 and β2 adrenoceptor antagonist, elevate regional serotonin synthesis in the rat brain: An autoradiographic study

机译：放射影像学研究发现，使用5-HT1A和β1和β2肾上腺素能受体拮抗剂匹多洛尔进行急性和亚慢性治疗均能提高大鼠脑区域5-羟色胺的合成。

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Antidepressant treatments, including those that increase serotonin (5-HT) neurotransmission, require several weeks or months until the onset of the therapeutic effect in depressed patients. The negative feedback on 5-HT transmission exhibited by the 5-HT1A and 5-HT1B autoreceptors has been postulated as a possible delaying factor. The aim of the present study was to assess the effect of the acute and subchronic treatment with pindolol, a 5-HT1A/1B, β1 and β2 adrenoceptor antagonist, on 5-HT synthesis, one of the key parameters of 5-HT neurotransmission. Male Sprague-Dawley (SPD) rats (180-220 g) were treated with pindolol or an adequate volume of saline, administered either acutely (15 mg/kg i.p.; SPD-AC-SAL, SPD-AC-TR) or subchronically (15 mg/kg day i.p. for 7 days; SPD-SUBCHR-SAL, SPD-SUBCHR-TR). Thirty minutes following the single i.p. injection (acute experiment) or at the 8th day following the commencement of the subchronic treatment (subchronic experiment), 5-HT synthesis was measured using α-[14C]methyl-l-tryptophan autoradiography. The analysis of variance (ANOVA), followed by the Benjamini-Hochberg correction for multiple comparisons, revealed: (1) a significant increase of 5-HT synthesis in the SPD-AC-TR rats, relative to the SPD-AC-SAL rats in all brain regions examined except the substantia nigra - pars reticularis, dorsal subiculum, inferior olive, raphe magnus and raphe obscurus and (2) a significant increase of 5-HT synthesis in the SPD-SUBCHR-TR rats, relative to the SPD-SUBCHR-SAL rats in all brain regions except the median raphe, hypothalamus and raphe pontine. On the basis of these results, we hypothesized that the antagonism of the 5-HT 1A/1B receptors prevents the negative feedback mediated by these receptors on 5-HT synthesis, resulting in a persistent increase of 5-HT synthesis. The results accord with clinical reports on the utility of pindolol in the augmentation of antidepressant treatment.
机译：抗抑郁药的治疗，包括增加5-羟色胺（5-HT）神经传递的治疗，需要数周或数月的时间，直到抑郁症患者开始发挥治疗作用。推测5-HT1A和5-HT1B自体受体表现出的对5-HT传输的负反馈是可能的延迟因素。本研究的目的是评估用5-HT1A / 1B，β1和β2肾上腺素能受体拮抗剂匹多洛尔进行的急性和亚慢性治疗对5-HT合成（5-HT神经传递的关键参数之一）的影响。雄性Sprague-Dawley（SPD）大鼠（180-220 g）用哌多洛尔或适量的生理盐水处理，急性给药（15 mg / kg ip; SPD-AC-SAL，SPD-AC-TR）或亚慢性（每天15 mg / kg ip，持续7天; SPD-SUBCHR-SAL，SPD-SUBCHR-TR）。单次i.p.后30分钟注射（急性实验）或在亚慢性治疗开始后的第8天（亚慢性实验），使用α-[14C]甲基-1-色氨酸放射自显影测量5-HT合成。方差分析（ANOVA），然后进行Benjamini-Hochberg校正以进行多次比较，发现：（1）SPD-AC-TR大鼠相对于SPD-AC-SAL大鼠，5-HT合成显着增加在所有检查过的脑区域中，除了黑质，网状背侧，下橄榄，下橄榄，大裂脑牛和暗裂牛脑，以及（2）SPD-SUBCHR-TR大鼠的5-HT合成相对于SPD- SUBCHR-SAL大鼠除脑中线，下丘脑和桥脑桥以外的所有区域。基于这些结果，我们假设5-HT 1A / 1B受体的拮抗作用阻止了这些受体介导的5-HT合成的负反馈，导致5-HT合成的持续增加。该结果与关于哌多洛尔在增强抗抑郁药治疗中的效用的临床报道相符。

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