Vilpoux Catherine, Warnault Vincent, Pierrefiche Olivier, Daoust Martine, Naassila Mickael
Equipe Région INSERM 24 (ERI24), Groupe de Recherche sur l'Alcool et les Pharmacodépendances, Université de Picardie Jules Verne, Faculté de Pharmacie, 1 rue des Louvels, Amiens, France.
Alcohol Clin Exp Res. 2009 Jun;33(6):945-69. doi: 10.1111/j.1530-0277.2009.00916.x. Epub 2009 Mar 19.
Ethanol addiction has been conceptualized as a progression from occasional, impulsive use to compulsive behavior. Ethanol-dependence is a chronic pathology with repeated cycles of withdrawal, craving, and relapse. Specific molecular and cellular mechanisms underlie these transition stages.
This review aimed at elucidating whether there are also adaptations in the pattern of brain regions responding to ethanol. This paper reviews the evidence in rodents for activation of specific brain regions, assessed by induction of IEG expression, following acute and chronic ethanol exposure.
The review sheds light on the specific patterns of response in regions of the brain to different types of ethanol exposure and shows that activation of specific brain regions may occur in particular phases of the development of ethanol addiction. Some brain regions respond consistently following acute or chronic treatments or withdrawal: the prefrontal cortex; nucleus accumbens; lateral septum; hippocampus; perioculomotor urocortin-containing cells population (pIIIu), also known as Edinger-Westphal nucleus; central nucleus of the amygdala; and the paraventricular nucleus of hypothalamus. The two last brain areas are particularly activated by relapse-inducing stressors. It is of interest that the amygdala, hippocampus, and prefrontal cortex, which belong to the reward system, are activated by cue-induced relapse to ethanol self-administration in rodents and humans, while activation of these regions is reversed with anti-craving compounds. Following chronic exposure, IEG induction desensitizes while withdrawal reactivates these regions.
Some responding regions are implicated in reward related processes (VTA, extended amygdala, hypothalamus, hippocampus, prelimbic cortex, ventral part of lateral septum) and some others in aversive-related processes (area postrema, nucleus of solitary tract).
A better understanding of the neural circuits affected by ethanol and their adaptations during the development of ethanol addiction will provide new opportunities for developing appropriate therapies.
乙醇成瘾已被概念化为一个从偶尔的冲动使用发展为强迫行为的过程。乙醇依赖是一种慢性病理状态，具有反复的戒断、渴望和复发周期。特定的分子和细胞机制是这些过渡阶段的基础。
本综述旨在阐明在对乙醇作出反应的脑区模式中是否也存在适应性变化。本文回顾了啮齿动物中急性和慢性乙醇暴露后通过诱导即刻早期基因（IEG）表达评估特定脑区激活的证据。
该综述揭示了大脑区域对不同类型乙醇暴露的特定反应模式，并表明特定脑区的激活可能发生在乙醇成瘾发展的特定阶段。一些脑区在急性或慢性治疗或戒断后始终有反应：前额叶皮层、伏隔核、外侧隔核、海马体、含促尿钠排泄肽的动眼神经周围细胞群（pIIIu，也称为动眼神经核）、杏仁核中央核和下丘脑室旁核。最后两个脑区尤其会被诱导复发的应激源激活。有趣的是，属于奖赏系统的杏仁核、海马体和前额叶皮层在啮齿动物和人类中会被线索诱导的乙醇自我给药复发激活，而这些区域的激活会被抗渴望化合物逆转。慢性暴露后，IEG诱导作用会脱敏，而戒断会使这些区域重新激活。
一些有反应的区域与奖赏相关过程有关（腹侧被盖区、扩展杏仁核、下丘脑、海马体、前边缘皮层、外侧隔核腹侧部分），而其他一些区域与厌恶相关过程有关（最后区、孤束核）。
更好地理解受乙醇影响的神经回路及其在乙醇成瘾发展过程中的适应性变化将为开发合适的治疗方法提供新机会。
