INCREASE OF NORADRENALINE RELEASE IN THE HYPOTHALAMUS OF FREELY MOVING RAT BY POSTSYNAPTIC 5-HYDROXYTRYPTAMINE(1A) RECEPTOR ACTIVATION

被引：68

作者：

SUZUKI, M ^{[1
]}

MATSUDA, T ^{[1
]}

ASANO, S ^{[1
]}

SOMBOONTHUM, P ^{[1
]}

TAKUMA, K ^{[1
]}

BABA, A ^{[1
]}

机构：

[1] OSAKA UNIV,FAC PHARMACEUT SCI,DEPT PHARMACOL,SUITA,OSAKA 565,JAPAN

来源：

BRITISH JOURNAL OF PHARMACOLOGY | 1995年 / 115卷 / 04期

关键词：

5-HYDROXYTRYPTAMINE (5-HT); 5-HT1A RECEPTORS; POSTSYNAPTIC; MKC-242; NORADRENALINE (NA) RELEASE; MICRODIALYSIS;

D O I：

10.1111/j.1476-5381.1995.tb14990.x

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

1 5-Hydroxytryptamine (5-HT) plays a role in the regulation of noradrenergic neurones in the brain, but the precise mechanism of regulation of noradrenaline (NA) release by 5-HT1A receptors has not been defined. The present study describes the effect of a highly potent and selective 5-HT1A receptor agonist, 5-{3-[[(2S)-1,4-benzodioxan-2-ylmethyl]amino]propoxy}-1,3-benzodioxole HCl (MKC-242), on NA release in the hypothalamus using microdialysis in the freely moving rat. 2 Subcutaneous injection of MKC-242 (0.5 mg kg(-1)) increased extracellular levels of NA and its metabolite, 3-methoxy-4-hydroxyphenylglycol, in the hypothalamus and hippocampus. 3 The 5-HT1A receptor agonists, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (0.2 mg kg(-1)) and buspirone (3 mg kg(-1)) mimicked the effect of MKC-242 in increasing NA release in the hypothalamus. 4 The effects of MKC-242 and 8-OH-DPAT in the hypothalamus were antagonized by pretreatment with WAY100135 (10 mg kg(-1)), a silent 5-HT1A receptor antagonist. 5 Local administration of 8-OH-DPAT (10-100 mu M), citalopram (1 mu M), a 5-HT reuptake inhibitor, and MDL72222 (10 mu M), a 5-HT3 receptor antagonist, into the hypothalamus, had no effect on NA release. 6 Intracerebroventricular injection with 5,7-dihydroxytryptamine caused a marked reduction in brain 5HT content, but the treatment affected neither basal NA levels nor the MKC-242-induced increase in NA release. 7 The effect of MKC-242 in increasing NA release was not attenuated by repeated treatment with the drug (0.5 mg kg(-1), once a day for 2 weeks). 8 The present results suggest that activation of postsynaptic 5-HT1A receptors increases NA release in the hypothalamus.

引用

页码：703 / 711

页数：9

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