Toalston Jamie E, Deehan Gerald A, Hauser Sheketha R, Engleman Eric A, Bell Richard L, Murphy James M, Truitt William A, McBride William J, Rodd Zachary A
Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, Indiana
Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, Indiana.
J Pharmacol Exp Ther. 2014 Nov;351(2):317-26. doi: 10.1124/jpet.114.218172. Epub 2014 Aug 22.
Alcohol drinking during adolescence is associated with increased alcohol drinking and alcohol dependence in adulthood. Research examining the biologic consequences of adolescent ethanol (EtOH) consumption on the response to EtOH in the neurocircuitry shown to regulate drug reinforcement is limited. The experiments were designed to determine the effects of periadolescent alcohol drinking on the reinforcing properties of EtOH within the posterior ventral tegmental area (pVTA) and the ability of EtOH microinjected into the pVTA to stimulate dopamine (DA) release in the nucleus accumbens shell (AcbSh). EtOH access (24-hour free-choice) by alcohol-preferring rats occurred during postnatal days (PND) 30-60. Animals were tested for their response to EtOH after PND 85. Intracranial self-administration techniques were performed to assess EtOH self-infusion into the pVTA. In the second experiment, rats received microinjections of EtOH into the pVTA, and dialysis samples were collected from the AcbSh. The results indicate that in rats that consumed EtOH during adolescence, the pVTA was more sensitive to the reinforcing effects of EtOH (a lower concentration of EtOH supported self-administration) and the ability of EtOH microinjected into the pVTA to stimulate DA release in the AcbSh was enhanced (sensitivity and magnitude). The data indicate that EtOH consumption during adolescence altered the mesolimbic DA system to be more sensitive and responsive to EtOH. This increase in the response to EtOH within the mesolimbic DA during adulthood could be part of biologic sequelae that are the basis for the deleterious effects of adolescent alcohol consumption on the rate of alcoholism during adulthood.
青春期饮酒与成年后饮酒量增加及酒精依赖有关。关于青春期乙醇（EtOH）摄入对神经回路中EtOH反应的生物学后果的研究有限，而该神经回路被证明可调节药物强化作用。这些实验旨在确定青春期前后饮酒对腹侧被盖区后部（pVTA）内EtOH强化特性的影响，以及向pVTA微量注射EtOH刺激伏隔核壳（AcbSh）中多巴胺（DA）释放的能力。嗜酒大鼠在出生后第30至60天可自由选择饮用EtOH（24小时）。在出生后第85天之后对动物进行EtOH反应测试。采用颅内自我给药技术评估EtOH向pVTA的自我输注情况。在第二个实验中，给大鼠向pVTA微量注射EtOH，并从AcbSh收集透析样本。结果表明，在青春期摄入EtOH的大鼠中，pVTA对EtOH的强化作用更敏感（较低浓度的EtOH即可支持自我给药），并且向pVTA微量注射EtOH刺激AcbSh中DA释放的能力增强（敏感性和释放量）。数据表明，青春期摄入EtOH会改变中脑边缘DA系统，使其对EtOH更敏感且反应更强烈。成年期内中脑边缘DA对EtOH反应的这种增强可能是生物学后遗症的一部分，而这些后遗症正是青春期饮酒对成年期酒精中毒发生率产生有害影响的基础。
