Action of harman (1-methyl-beta-carboline) on the brain: Body temperature and in vivo efflux of 5-HT from hippocampus of the rat

Action of harman (1-methyl-beta-carboline) on the brain: Body temperature and in vivo efflux of 5-HT from hippocampus of the rat
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DOI:
10.1016/s0028-3908(96)00043-3
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发表时间:
1996-01-01
期刊:
影响因子:
4.7
通讯作者:
Myers, RD
Myers, RD
中科院分区:
医学2区
文献类型:
--
作者:
Adell, A;Biggs, TA;Myers, RD

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Harman(1-甲基-β-Caroline)此前已被证明作用于大鼠的海马体,其作用方式是唤起焦虑反应和诱导酒精偏好。在本实验中,在自由活动大鼠的背侧海马区局部灌流200 mU M Harman可增加脑透析液中5-羟色胺(5-HT)的含量,但不增加5-羟基吲哚乙酸(5-HIAA)的含量。全身给药5.0-20 mg/kg时,灌流液中5-羟色胺含量增加,但5-HIAA含量降低,且呈剂量依赖关系,可能与抑制单胺氧化酶A型酶(MAO-A)有关。哈曼以2.5-20 mg/kg的剂量全身给药可引起强烈的体温下降,其中5.0 mg/kg剂量的降温作用最大。5.0 mg/kg的(+/-)-吲哚洛尔不能拮抗5.0 mg/kg酒保引起的体温下降。此外,用对氯苯丙氨酸(PCPA)预处理大鼠也不能改变Barman诱导的体温下降。全身注射MAO-A抑制剂Clorgyline 10 mg/kg也能显著降低T-b。总体而言,目前的实验表明,哈曼显然通过抑制MAO-A的作用影响了大脑中的5-羟色胺系统。这一特性可能也是哈曼诱导的大鼠海马区5-羟色胺增加的原因。版权所有(C)1996爱思唯尔科学有限公司。
Harman (1-methyl-beta-carboline) has been shown previously to act on the hippocampus of the rat in terms of its evocation of anxiogenic responses and induction of alcohol preference. In the present experiments, the localized perfusion of 200 mu M harman in the dorsal hippocampus of freely moving rats increased the levels of serotonin (5-HT) but not 5-hydroxyindoleacetic acid (5-HIAA) in cerebral dialysates. The systemic administration of 5.0-20 mg/kg harman also enhanced 5-HT in the perfusates but reduced the levels of 5-HIAA in a dose-dependent manner, probably as a result of the inhibition of the enzyme monoamine oxidase type A (MAO-A). Harman given systemically in doses of 2.5-20 mg/kg induced an intense hypothermia, with a maximum fall produced by the 5.0 mg/kg dose. This fall in body temperature (T-b) induced by 5.0 mg/kg barman was not antagonized by 5.0 mg/kg of (+/-)-pindolol. Further, pretreatment of the rats with parachlorophenylalanine (pCPA) also failed to alter the barman-induced hypothermia. The systemic administration of 10 mg/kg of the MAO-A inhibitor, clorgyline, also lowered T-b significantly. Overall, the present experiments show that harman apparently influences 5-HT systems in the brain by its action in inhibiting MAO-A. This property is likely responsible also for the harman-induced increase of 5-HT in the hippocampus of the rats. Copyright (C) 1996 Elsevier Science Ltd.