Israel Yedy, Karahanian Eduardo, Ezquer Fernando, Morales Paola, Ezquer Marcelo, Rivera-Meza Mario, Herrera-Marschitz Mario, Quintanilla María E
Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, University of ChileSantiago, Chile.
Center for Biomedical Research, Universidad Autónoma de ChileSantiago, Chile.
Front Behav Neurosci. 2017 Apr 4;11:57. doi: 10.3389/fnbeh.2017.00057. eCollection 2017.
This review article addresses the biological factors that influence: (i) the of alcohol intake; (ii) the of chronic alcohol intake; and (iii) drinking behavior in animals bred for their high-ethanol intake. Data from several rat strains/lines strongly suggest that catalase-mediated brain oxidation of ethanol into acetaldehyde is an absolute requirement (up 80%-95%) for rats to display ethanol's reinforcing effects and to initiate chronic ethanol intake. Acetaldehyde binds non-enzymatically to dopamine forming salsolinol, a compound that is self-administered. In UChB rats, salsolinol: (a) generates marked sensitization to the motivational effects of ethanol; and (b) strongly promotes binge-like drinking. The specificity of salsolinol actions is shown by the finding that only the R-salsolinol enantiomer but not S-salsolinol accounted for the latter effects. Inhibition of brain acetaldehyde synthesis does not influence the of chronic ethanol intake. However, a prolonged ethanol withdrawal partly returns the requirement for acetaldehyde synthesis/levels both on chronic ethanol intake and on alcohol relapse-like drinking. Chronic ethanol intake, involving the action of lipopolysaccharide diffusing from the gut, and likely oxygen radical generated upon catechol/salsolinol oxidation, leads to oxidative stress and neuro-inflammation, known to potentiate each other. Data show that the administration of N-acetyl cysteine (NAC) a strong antioxidant inhibits chronic ethanol by 60%-70%, without inhibiting its initial intake. Intra-cerebroventricular administration of mesenchymal stem cells (MSCs), known to release anti-inflammatory cytokines, to elevate superoxide dismutase levels and to reverse ethanol-induced hippocampal injury and cognitive deficits, also inhibited chronic ethanol maintenance; further, was inhibited up to 85% for 40 days following intracerebral stem cell administration. Thus: (i) ethanol must be metabolized intracerebrally into acetaldehyde, and further into salsolinol, which appear responsible for promoting the of the early reinforcing effects of ethanol; (ii) acetaldehyde is not responsible for the of chronic ethanol intake, while other mechanisms are indicated; (iii) the systemic administration of NAC, a strong antioxidant markedly inhibits the of chronic ethanol intake; and (iv) the intra-cerebroventricular administration of anti-inflammatory and antioxidant MSCs inhibit both the of chronic ethanol intake and .
（i）酒精摄入的[具体内容缺失]；（ii）慢性酒精摄入的[具体内容缺失]；以及（iii）为高乙醇摄入量而培育的动物的饮酒行为。来自多个大鼠品系/品系的数据强烈表明，过氧化氢酶介导的大脑中将乙醇氧化为乙醛的过程是大鼠表现出乙醇强化作用并开始慢性乙醇摄入的绝对必要条件（高达80%-95%）。乙醛与多巴胺非酶促结合形成salsolinol，一种可自我给药的化合物。在UChB大鼠中，salsolinol：（a）对乙醇的动机效应产生明显的敏化作用；（b）强烈促进类似暴饮的饮酒行为。salsolinol作用的特异性体现在只有R-salsolinol对映体而非S-salsolinol产生了后者的效应这一发现上。抑制大脑乙醛合成并不影响慢性乙醇摄入的[具体内容缺失]。然而，长期乙醇戒断在一定程度上恢复了对乙醛合成/水平在慢性乙醇摄入和类似酒精复饮行为上的需求。慢性乙醇摄入涉及从肠道扩散的脂多糖的作用，以及儿茶酚/salsolinol氧化时可能产生的氧自由基，导致氧化应激和神经炎症，已知二者会相互增强。数据表明，给予强抗氧化剂N-乙酰半胱氨酸（NAC）可将慢性乙醇[具体内容缺失]抑制60%-70%，而不抑制其初始摄入。脑室内给予间充质干细胞（MSCs），已知其可释放抗炎细胞因子，提高超氧化物歧化酶水平并逆转乙醇诱导的海马损伤和认知缺陷，也抑制了慢性乙醇维持；此外，在脑内干细胞给药后40天内[具体内容缺失]被抑制高达85%。因此：（i）乙醇必须在脑内代谢为乙醛，进而代谢为salsolinol，它们似乎负责促进乙醇早期强化作用的[具体内容缺失]；（ii）乙醛不负责慢性乙醇摄入的[具体内容缺失]，而提示了其他机制；（iii）给予强抗氧化剂NAC进行全身给药可显著抑制慢性乙醇摄入的[具体内容缺失]；以及（iv）脑室内给予抗炎和抗氧化的MSCs可抑制慢性乙醇摄入的[具体内容缺失]和[具体内容缺失]。
