Pereira Pedro A, Neves João, Vilela Manuel, Sousa Sérgio, Cruz Catarina, Madeira M Dulce
Department of Anatomy, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal.
Neurotoxicol Teratol. 2014 Jul-Aug;44:53-61. doi: 10.1016/j.ntt.2014.05.007. Epub 2014 Jun 2.
Neuropeptide Y (NPY)- and acetylcholine-containing interneurons of the nucleus accumbens (NAc) seem to play a major role in the rewarding effects of alcohol. This study investigated the relationship between chronic alcohol consumption and subsequent withdrawal and the expression of NPY and acetylcholine in the NAc, and the possible involvement of nerve growth factor (NGF) in mediating the effects of ethanol. Rats ingesting an aqueous ethanol solution over 6months and rats subsequently deprived from ethanol during 2months were used to estimate the total number and the somatic volume of NPY and cholinergic interneurons, and the numerical density of cholinergic varicosities in the NAc. The tissue content of choline acetyltransferase (ChAT) and catecholamines were also determined. The number of NPY interneurons increased during alcohol ingestion and returned to control values after withdrawal. Conversely, the number and the size of cholinergic interneurons, and the amount of ChAT were unchanged in ethanol-treated and withdrawn rats, but the density of cholinergic varicosities was reduced by 50% during alcohol consumption and by 64% after withdrawal. The concentrations of dopamine and norepinephrine were unchanged both during alcohol consumption and after withdrawal. The administration of NGF to withdrawn rats significantly increased the number of NPY-immunoreactive neurons, the size of cholinergic neurons and the density of cholinergic varicosities. Present data show that chronic alcohol consumption leads to long-lasting neuroadaptive changes of the cholinergic innervation of the NAc and suggest that the cholinergic system is a potential target for the development of therapeutic strategies in alcoholism and abstinence.
伏隔核（NAc）中含神经肽Y（NPY）和乙酰胆碱的中间神经元似乎在酒精的奖赏效应中起主要作用。本研究调查了长期饮酒及随后戒酒与NAc中NPY和乙酰胆碱表达之间的关系，以及神经生长因子（NGF）在介导乙醇作用中可能的参与情况。将摄入含水乙醇溶液6个月的大鼠以及随后2个月剥夺乙醇的大鼠用于估计NAc中NPY和胆碱能中间神经元的总数和胞体体积，以及胆碱能曲张体的数值密度。还测定了胆碱乙酰转移酶（ChAT）和儿茶酚胺的组织含量。饮酒期间NPY中间神经元数量增加，戒酒后恢复到对照值。相反，乙醇处理和戒断大鼠中胆碱能中间神经元的数量和大小以及ChAT的量没有变化，但饮酒期间胆碱能曲张体的密度降低了50%，戒断后降低了64%。饮酒期间和戒断后多巴胺和去甲肾上腺素的浓度均未改变。给戒断大鼠注射NGF可显著增加NPY免疫反应性神经元的数量、胆碱能神经元的大小和胆碱能曲张体的密度。目前的数据表明，长期饮酒会导致NAc胆碱能神经支配发生持久的神经适应性变化，并表明胆碱能系统是酒精中毒和戒酒治疗策略开发的潜在靶点。
