Department of Neuroscience, Mahoney Institute for Neurosciences, Perelman School for Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Neuroscience, Mahoney Institute for Neurosciences, Perelman School for Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cell Rep. 2018 Apr 3;23(1):68-77. doi: 10.1016/j.celrep.2018.03.030.
Adolescent smoking is associated with pathological drinking later in life, but the biological basis for this vulnerability is unknown. To examine how adolescent nicotine exposure influences subsequent ethanol intake, nicotine was administered during adolescence or adulthood, and responses to alcohol were measured 1 month later. We found that adolescent, but not adult, nicotine exposure altered GABA signaling within the ventral tegmental area (VTA) and led to a long-lasting enhancement of alcohol self-administration. We detected depolarizing shifts in GABA reversal potentials arising from impaired chloride extrusion in VTA GABA neurons. Alterations in GABA signaling were dependent on glucocorticoid receptor activation and were associated with attenuated dopaminergic neuron responses to alcohol in the lateral VTA. Importantly, enhancing chloride extrusion in adolescent nicotine-treated animals restored VTA GABA signaling and alcohol self-administration to control levels. Taken together, this work suggests that adolescent nicotine exposure increases the risk profile for increased alcohol drinking in adulthood.
青少年吸烟与日后的病理性饮酒有关，但这种易感性的生物学基础尚不清楚。为了研究青少年尼古丁暴露如何影响随后的乙醇摄入，在青少年期或成年期给予尼古丁，并在 1 个月后测量对酒精的反应。我们发现，只有青少年期的尼古丁暴露改变了腹侧被盖区（VTA）中的 GABA 信号传递，导致酒精自我给药的持久增强。我们检测到 VTA GABA 神经元中氯离子外排受损导致 GABA 反转电位出现去极化漂移。GABA 信号的改变依赖于糖皮质激素受体的激活，并与外侧 VTA 中多巴胺能神经元对酒精的反应减弱有关。重要的是，增强青少年期尼古丁处理动物的氯离子外排可使 VTA GABA 信号传递和酒精自我给药恢复到对照水平。综上所述，这项工作表明，青少年期尼古丁暴露增加了成年后饮酒量增加的风险。
