Neuroscience Graduate Program, Vanderbilt University, Nashville, Tennessee, USA.
Biol Psychiatry. 2011 Sep 15;70(6):583-92. doi: 10.1016/j.biopsych.2011.03.035. Epub 2011 May 14.
Administration of cocaine during adolescence alters neurotransmission and behavioral sensitization in adulthood, but the effect on the acquisition of fear memories and the development of emotion-based neuronal circuits is unknown.
We examined fear learning and anxiety-related behaviors in adult male rats that were subjected to binge cocaine treatment during adolescence. We furthermore conducted gene expression analyses of the amygdala 22 hours after the last cocaine injection to identify molecular patterns that might lead to altered emotional processing.
Rats injected with cocaine during adolescence displayed less anxiety in adulthood than their vehicle-injected counterparts. In addition, cocaine-exposed animals were deficient in their ability to develop contextual fear responses. Cocaine administration caused transient gene expression changes in the Wnt signaling pathway, of axon guidance molecules, and of synaptic proteins, suggesting that cocaine perturbs dendritic structures and synapses in the amygdala. Phosphorylation of glycogen synthase kinase 3 beta, a kinase in the Wnt signaling pathway, was altered immediately following the binge cocaine paradigm and returned to normal levels 22 hours after the last cocaine injection.
Cocaine exposure during adolescence leads to molecular changes in the amygdala and decreases fear learning and anxiety in adulthood.
青春期滥用可卡因会改变成年后的神经传递和行为敏感化，但它对恐惧记忆的获得和情绪相关神经元回路的发展的影响尚不清楚。
我们检查了在青春期接受可卡因 binge 治疗的成年雄性大鼠的恐惧学习和与焦虑相关的行为。我们还在最后一次可卡因注射后 22 小时对杏仁核进行了基因表达分析，以确定可能导致情绪处理改变的分子模式。
青春期接受可卡因注射的大鼠在成年后表现出较少的焦虑。此外，暴露于可卡因的动物在发展情境性恐惧反应方面存在缺陷。可卡因给药导致 Wnt 信号通路、轴突导向分子和突触蛋白的基因表达发生短暂变化，表明可卡因扰乱了杏仁核中的树突结构和突触。糖原合成激酶 3β（Wnt 信号通路中的一种激酶）的磷酸化在 binge 可卡因范式后立即发生改变，并在最后一次可卡因注射后 22 小时恢复正常水平。
青春期暴露于可卡因会导致杏仁核中的分子变化，并减少成年后的恐惧学习和焦虑。
