Elucidating the biological basis for the reinforcing actions of alcohol in the mesolimbic dopamine system: the role of active metabolites of alcohol.
Elucidating the biological basis for the reinforcing actions of alcohol in the mesolimbic dopamine system: the role of active metabolites of alcohol.
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DOI：
10.3389/fnbeh.2013.00104
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发表时间：
2013
影响因子：
3
通讯作者：
Rodd ZA
中科院分区：
文献类型：
--
作者：
Deehan GA Jr;Hauser SR;Wilden JA;Truitt WA;Rodd ZA
酒精中毒治疗药物的成功开发取决于对酒精生物学作用的理解。酒精研究领域的一个局限性是只研究酒精的作用，而忽视了酒精的多种生物活性代谢产物。酒精是一种“前药”的概念并不新鲜。酒精在大脑中很容易代谢成乙醛。乙醛是一种高反应性化合物，可形成多种缩合产物，包括猪毛菜醇和异猪毛菜醇（乙醛和多巴胺）。最近的实验已经确定，酒精的许多代谢产物具有直接的CNS作用，并且可以部分或全部介导酒精在中脑边缘多巴胺系统内的增强作用。中脑边缘多巴胺系统起源于腹侧被盖区（VTA），并投射到前脑区域，包括丘脑核（Acb）和内侧前额叶皮层（mPFC），被认为是控制滥用药物的奖励特性的神经回路。在这种神经回路中，有令人信服的证据表明;（1）酒精的生物活性代谢物可以直接或间接增加腹侧被盖区多巴胺神经元的活性，（2）酒精和酒精代谢物在中脑边缘多巴胺系统内增强，（3）抑制酒精代谢途径抑制酒精暴露的生物后果，（4）可以通过抑制/减弱中脑边缘多巴胺系统中的酒精代谢途径来减少酒精消耗，（5）酒精代谢物可以改变中脑边缘多巴胺系统中的神经化学水平，和（6）酒精与酒精代谢物相互作用以增强两种化合物的作用。这些数据表明，酒精和酒精代谢物之间存在正相关关系，可以调节饮酒的生物后果以及酒精使用升级为酒精中毒的可能性。
The development of successful pharmacotherapeutics for the treatment of alcoholism is predicated upon understanding the biological action of alcohol. A limitation of the alcohol research field has been examining the effects of alcohol only and ignoring the multiple biological active metabolites of alcohol. The concept that alcohol is a “pro-drug” is not new. Alcohol is readily metabolized to acetaldehyde within the brain. Acetaldehyde is a highly reactive compound that forms a number of condensation products, including salsolinol and iso-salsolinol (acetaldehyde and dopamine). Recent experiments have established that numerous metabolites of alcohol have direct CNS action, and could, in part or whole, mediate the reinforcing actions of alcohol within the mesolimbic dopamine system. The mesolimbic dopamine system originates in the ventral tegmental area (VTA) and projects to forebrain regions that include the nucleus accumbens (Acb) and the medial prefrontal cortex (mPFC) and is thought to be the neurocircuitry governing the rewarding properties of drugs of abuse. Within this neurocircuitry there is convincing evidence that; (1) biologically active metabolites of alcohol can directly or indirectly increase the activity of VTA dopamine neurons, (2) alcohol and alcohol metabolites are reinforcing within the mesolimbic dopamine system, (3) inhibiting the alcohol metabolic pathway inhibits the biological consequences of alcohol exposure, (4) alcohol consumption can be reduced by inhibiting/attenuating the alcohol metabolic pathway in the mesolimbic dopamine system, (5) alcohol metabolites can alter neurochemical levels within the mesolimbic dopamine system, and (6) alcohol interacts with alcohol metabolites to enhance the actions of both compounds. The data indicate that there is a positive relationship between alcohol and alcohol metabolites in regulating the biological consequences of consuming alcohol and the potential of alcohol use escalating to alcoholism.
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DOI：
10.1111/j.1530-0277.1998.tb03644.x
发表时间：
1998-02-01
影响因子：
3.2
作者：
Brodie, MS;Appel, SB
通讯作者：
Appel, SB
DOI：
10.1111/j.1530-0277.1980.tb04833.x
发表时间：
1980-01-01
影响因子：
3.2
作者：
COHEN, G;SINET, PM;HEIKKILA, R
通讯作者：
HEIKKILA, R
影响因子：
56.9
作者：
COHEN, G;COLLINS, M
通讯作者：
COLLINS, M
影响因子：
6.1
作者：
ARAGON, CMG;SPIVAK, K;AMIT, Z
通讯作者：
AMIT, Z
影响因子：
4.4
作者：
ADELL, A;MYERS, RD
通讯作者：
MYERS, RD