Departamento de Neuroquímica, Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría Ramón de la Fuente, Ciudad de México, México.
Departamento de Neuroquímica, Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría Ramón de la Fuente, Ciudad de México, México.
Vitam Horm. 2019;111:313-337. doi: 10.1016/bs.vh.2019.05.005. Epub 2019 Jun 10.
Endogenous opioids (enkephalins, endorphins and dynorphins) are small peptides that play a main role in pain perception and analgesia, as well as in alcohol (ethanol) reinforcement and reward. Alcohol reinforcement involves the ethanol-induced activation of the endogenous opioid system, a process that may augment the hedonic value and the reinforcing properties of the drug, which in turn increases substance consumption. Changes in opioidergic transmission may contribute to alcohol intoxication and to the neuroadaptive responses produced by the long-lasting exposure to ethanol. Opioidergic transmission may be altered by ethanol at distinct levels, including the expression of precursor mRNAs, biosynthesis and release of opioid peptides, as well as ligand binding to opioid receptors. In adult rats, β-endorphinergic and enkephalinergic transmission, through activation of mu and delta opioid receptors, mediate ethanol reinforcement and high alcohol drinking behavior. Prenatal ethanol exposure (PEE) selectively modifies Methionine-enkephalin (Met-enk) content in several brain regions of infant and adolescent rats, particularly those of the reward circuits. In preweanling rats, Met-enk content is decreased in the ventral tegmental area but is increased in the prefrontal cortex and the nucleus accumbens and other brain areas, as a consequence of a short and moderate ethanol exposure during late gestation. PEE also increases Met-enk levels in the prefrontal cortex and other brain regions of 30-day-old adolescent rats. These findings suggest that mesocorticolimbic enkephalins are essential in ethanol reinforcement in offspring, as previously reported in adult rats.
内源性阿片肽（脑啡肽、内啡肽和强啡肽）是在疼痛感知和镇痛以及酒精（乙醇）强化和奖赏中起主要作用的小肽。酒精强化涉及内源性阿片肽系统的乙醇诱导激活，这一过程可能增加药物的愉悦值和强化特性，从而增加物质消耗。阿片肽传递的变化可能有助于酒精中毒和长期暴露于乙醇产生的神经适应性反应。阿片肽传递可能在不同水平上被乙醇改变，包括前体 mRNA 的表达、阿片肽的生物合成和释放，以及配体与阿片受体的结合。在成年大鼠中，β-内啡肽能和脑啡肽能通过激活μ和δ阿片受体来介导乙醇强化和高酒精饮用量。产前乙醇暴露（PEE）选择性地改变了幼鼠和青少年大鼠的几个脑区的亮氨酸脑啡肽（Met-enk）含量，特别是奖励回路的脑区。在新生大鼠中，Met-enk 含量在腹侧被盖区减少，但在前额叶皮质和伏隔核和其他脑区增加，这是由于在妊娠晚期短暂和适度的乙醇暴露。PEE 还增加了 30 日龄青少年大鼠前额皮质和其他脑区的 Met-enk 水平。这些发现表明，中脑边缘阿片肽在后代的乙醇强化中是必不可少的，这与之前在成年大鼠中的研究结果一致。
