5-HT, DOPAMINE, NOREPINEPHRINE, AND RELATED METABOLITES IN BRAIN OF LOW ALCOHOL-DRINKING (LAD) RATS SHIFT AFTER CHRONIC INTRAHIPPOCAMPAL INFUSION OF HARMAN
5-HT, DOPAMINE, NOREPINEPHRINE, AND RELATED METABOLITES IN BRAIN OF LOW ALCOHOL-DRINKING (LAD) RATS SHIFT AFTER CHRONIC INTRAHIPPOCAMPAL INFUSION OF HARMAN
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DOI：
10.1007/bf00970546
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发表时间：
1995-02-01
影响因子：
4.4
通讯作者：
MYERS, RD
中科院分区：
文献类型：
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作者：
ADELL, A;MYERS, RD
哈曼（1-甲基-β-咔啉）已被证明可以诱导遗传育种的低酒精饮用（LAD）大鼠对酒精的偏好。本研究在LAD大鼠中进行，以确定是否单胺及其代谢产物在不同区域的大脑被哈曼慢性注入背海马改变。为此，将套管立体定位植入背侧海马。将套管连接到皮下植入肩胛骨内空间的渗透微型泵。该泵填充有人工脑脊液（CSF）载体或Harman，其以1.0或3.0 μ g/h的速率输送（即，5.5或16.5nmol/h）持续14天。手术后4天，在10天内对大鼠进行乙醇的标准偏好测试，其中浓度每天从3%增加到30%。较高浓度的barman注入海马升高5-羟色胺（5-HT）的水平，无论是同侧和对侧的海马部位的输液，以及在中脑，额叶皮质，纹状体和丘脑核。同样，这种处理导致海马和中脑中去甲肾上腺素水平升高，但围栏中多巴胺水平降低。在给予3.0 μ g/h哈曼的大鼠围栏中，5-羟基吲哚乙酸（5-HIAA）和3，4-二羟基苯乙酸（DOPAC）的水平降低，而两种浓度的β-咔啉均降低了额叶皮层中高香草酸（HVA）的水平。这些哈曼诱导的胺代谢的变化可能是单胺氧化酶（MAO）的抑制的结果。当哈曼引起的神经化学值的变化与先前报道的大鼠酒精摄入量相比时，没有发现显著的相关性，这种一致性的缺乏表明哈曼产生的单胺神经递质的改变和β-咔啉引起的酒精自愿摄入可能不是源于大脑中的同一系统。
Harman (1-methyl-beta-carboline) has been shown to induce preference for alcohol in the genetically bred, low alcohol drinking (LAD) rat. This study was undertaken in the LAD rat to determine whether monoamines and their metabolites in different regions of the brain are altered by harman infused chronically into the dorsal hippocampus. For this purpose, a cannula was implanted stereotaxically into the dorsal hippocampus. The cannula was attached to an osmotic minipump implanted subcutaneously within the intrascapular space. The pump was filled with either an artificial cerebrospinal fluid (CSF) vehicle or harman, which was delivered at a rate of 1.0 or 3.0 mu g/h (i.e., 5.5 or 16.5 nmol/h, respectively) for a period of 14 days. Four days after surgery, a standard preference test for ethyl alcohol was given to the rats over 10 days in which concentrations were increased daily from 3%-30%. The higher concentration of barman infused into the hippocampus elevated the level of serotonin (5-HT), both ipsilateral and contralateral to the hippocampal site of infusion, as well as in the midbrain, frontal cortex, striatum and nucleus accumbens. Similarly, this treatment resulted in a rise in the levels of norepinephrine in the hippocampus and midbrain but decreases in dopamine levels in the pens. The levels of 5-hydroxyindoleacetic acid (5-HIAA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were diminished in the pens of rats given 3.0 mu g/h harman, whereas both concentrations of the beta-carboline reduced the level of homovanillic acid (HVA) in the frontal cortex. These harman-induced changes in the metabolism of the amines are possibly the result of an inhibition of monoamine oxidase (MAO). When the harman-induced shifts in the neurochemical values were compared to the alcohol intakes of the rats as reported previously, no significant correlation was found. The absence of this concordance suggests that the alterations in the monoamine neurotransmitters produced by harman and the voluntary intake of alcohol induced by this beta-carboline may not originate from the same systems in the brain.