Effects of mCPP on the extracellular concentrations of serotonin and dopamine in rat brain

Effects of mCPP on the extracellular concentrations of serotonin and dopamine in rat brain
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DOI:
10.1016/s0893-133x(98)00070-0
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发表时间:
1999-03-01
影响因子:
7.6
通讯作者:
Nissbrandt, H
Nissbrandt, H
中科院分区:
医学1区
文献类型:
--
作者:
Eriksson, E;Engberg, G;Nissbrandt, H

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在自发性高血压(SH)品系的清醒雄性Wistar大鼠中,采用体内微透析法测定,静脉注射间氯苯哌嗪(mCPP)(0.25或2.5 mg/kg)可诱导海马区细胞外5-羟色胺浓度显著且呈剂量相关性增加(基线的300- 1,400%)。表明mCPP的作用是由5-羟色胺转运蛋白的逆转引起的,它被5-羟色胺再摄取抑制剂西酞普兰(10 mg/kg)预处理所拮抗,但不受钠通道阻断剂河豚毒素(TTX; 1 μ m)局部给药的影响。mCPP还显示可诱导SH大鼠的脑桥核和纹状体以及Sprague-Dawley(SD)品系大鼠的脑桥核中多巴胺的细胞外浓度增加;然而,mCPP的这种作用比对5-羟色胺的作用弱得多(基线的125-170%);此外,它似乎是TTX敏感的。在麻醉的SD mts中,mCPP诱导黑质多巴胺细胞放电率中度降低;支持这种效应继发于所观察到的多巴胺释放增加的假设,其通过多巴胺合成抑制剂α-甲基-对-酪氨酸或多巴胺D-2受体拮抗剂氟哌啶醇预处理而被阻断。总之,结果表明,mCPP诱导MT脑中5-羟色胺释放的显着的,TTX不敏感的增加,但仅适度和TTX敏感的细胞外多巴胺水平的增加。[Neuropsychopharmacology 20:287-296,1999](C)1999年美国神经精神药理学学会。出版社:Elsevier Science Inc.
Intravenous administration of m-chloro-phenylpiperazine (mCPP) (0.25 or 2.5 mg/kg) induced a marked and dose-related increase in extracellular concentrations of serotonin in hippocampus (300-1,400% of baseline) as measured using in vivo microdialysis in awake male Wistar rats of the spontaneously hypertensive (SH) strain. indicating that the effect of mCPP was caused by a reversal of the serotonin transporter, it was antagonized by pretreatment with the serotonin re-uptake inhibitor citalopram (10 mg/kg) but was unaffected by local administration of the sodium channel blocker tetrodotoxin (TTX; 1 mu m). mCPP wits also shown to induce an increase in extracellular concentrations of dopamine in the nucleus accumbens and the striatum of SH rats and in the nucleus accumbens of rats of the Sprague-Dawley (SD) strain; this effect of mCPP was, however, much weaker (125-170% of baseline) than the effect on serotonin; moreover, it seems to be TTX-sensitive. In anesthetized SD mts, mCPP induced a moderate reduction of nigral dopamine cell firing rate; supporting the assumption that this effect is secondary to the observed increase in dopamine release, it was blocked by pretreatment either with the dopamine synthesis inhibitor alpha-methyl-para-tyrosine or with the dopamine D-2 receptor antagonist haloperidol. In conclusion, the results suggest that mCPP induces a marked, TTX-insensitive increase in serotonin release in mt brain, but only a modest and TTX-sensitive increase in the extracellular levels of dopamine. [Neuropsychopharmacology 20:287-296, 1999] (C) 1999 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.