Ethanol intake increases galanin mRNA in the hypothalamus and withdrawal decreases it

Ethanol intake increases galanin mRNA in the hypothalamus and withdrawal decreases it
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DOI:
10.1016/s0031-9384(03)00110-0
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发表时间:
2003-06-01
影响因子:
2.9
通讯作者:
Hoebel, BG
Hoebel, BG
中科院分区:
医学3区
文献类型:
--
作者:
Leibowitz, SF;Avena, NM;Hoebel, BG

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酒精中毒可以被看作是一种动机障碍,是由于大脑系统的摄食行为发生了变化。因此,假设酒精摄入可能会改变刺激进食的下丘脑肽的表达。早期的研究表明,下丘脑注射摄食刺激肽甘丙肽(GAL),增加了多巴胺(DA)在延髓核(NAc)中的释放,全身酒精也是如此,导致对GAL的关注。结果表明:(1)连续7天每天注射0.8g/kg 10%v/v乙醇,可显著增加GAL的表达,但对神经肽Y(neuropeptide Y,NPY)的表达无明显影响。这发生在特定的下丘脑核团,即背内侧核(DMN),室旁核(PVN)和穹窿周围外侧下丘脑(PLH)。(2)诱导大鼠自由饮用乙醇,逐渐增加浓度从1%到9%v/v,不加糖或调味品,表现出类似的刺激GAL mRNA的PVN和GAL免疫反应的DMN和PVN。(3)给予增加的乙醇浓度的大鼠,从4小时进入黑暗周期开始12小时,平均血液酒精浓度为18 mg/dl,并在DMN和PVN中表现出类似的GAL表达增加。(4)通过注射纳洛酮(3 mg/kg sc)产生的9%乙醇的阿片样物质效应的戒断,通过显著降低DMN和PLH中GAL表达至基线水平以下来逆转这种乙醇效应。这些研究表明下丘脑GAL在酒精滥用中可能起作用。(C)2003年爱思唯尔科学公司All rights reserved.
Alcoholism can be viewed as a motivational disorder that results from alterations in brain systems for ingestive behavior. Therefore, it was hypothesized that alcohol intake might alter the expression of hypothalamic peptides that stimulate feeding. Earlier studies showed that hypothalamic injection of the feeding-stimulatory peptide, galanin (GAL), increases the release of dopamine (DA) in the nucleus accumbens (NAc), as does systemic alcohol, leading to a focus on GAL. Results of this study demonstrate the following: (1) Ethanol, injected daily (0.8 g/kg 10% v/v) for 7 days in male rats, markedly increased the expression of GAL but not of neuropeptide Y (NPY). This occurred in specific hypothalamic nuclei, namely the dorsomedial nucleus (DMN), paraventricular nucleus (PVN) and perifornical lateral hypothalamus (PLH). (2) Rats induced to drink ethanol ad libitum, by gradually increasing the concentration from 1% to 9% v/v without adding sugar or flavoring, exhibited a similar stimulation of GAL mRNA in the PVN and GAL immunoreactivity in the DMN and PVN. (3) Rats given increasing ethanol concentrations, with 12 h access starting 4 h into the dark cycle, had a mean blood alcohol concentration of 18 mg/dl and exhibited a similar increase in GAL expression in the DMN and PVN. (4) Withdrawal from the opioid effects of 9% ethanol, produced by injection of naloxone (3 mg/kg sc), reversed this ethanol effect by significantly reducing GAL expression in the DMN and PLH below baseline levels. These studies suggest a possible role for hypothalamic GAL in alcohol abuse. (C) 2003 Elsevier Science Inc. All rights reserved.