Ye Tony, Pozos Hilda, Phillips Tamara J, Izquierdo Alicia
University of California, Los Angeles, Department of Psychology, Los Angeles, CA, USA.
Oregon Health & Science University, Veterans Affairs Medical Center and Methamphetamine Abuse Research Center, Portland, OR, USA.
Drug Alcohol Depend. 2014 May 1;138:17-23. doi: 10.1016/j.drugalcdep.2014.02.021. Epub 2014 Feb 26.
Flexible cognition is a set of processes mediated by the prefrontal cortex (PFC), an area of the brain that continues to develop during adolescence and into adulthood. Adult rodents exhibit impairments specific to reversal learning across various dosing regimens of methamphetamine (mAMPH). For adolescent rodents, ongoing PFC development can be assessed by discrimination reversal learning, a task dependent on frontostriatal integrity. The task may also index an increased vulnerability for mAMPH sampling in adulthood.
The purpose of the present study was to investigate the long-term effects of escalating, adolescent mAMPH exposure on reversal learning, a PFC-dependent task (Experiment 1) and the likelihood of later sampling of mAMPH in adulthood (Experiment 2).
Unlike previous research in adult-treated rats, our results show more generalized learning impairments after adolescent mAMPH exposure to include both attenuated visual discrimination as well as reversal learning. Additionally, we found that rats pre-exposed to mAMPH during adolescence consumed significantly more drug in adulthood. Intake of mAMPH was positively correlated with this learning. Taken together, these findings show that even modest exposure to mAMPH during adolescence may induce general learning impairments in adulthood, and an enduring sensitivity to the effects of mAMPH.
灵活认知是由前额叶皮层（PFC）介导的一组过程，前额叶皮层是大脑中一个在青春期持续发育直至成年的区域。成年啮齿动物在接受各种剂量方案的甲基苯丙胺（mAMPH）后，在逆向学习方面表现出特定的损伤。对于青春期啮齿动物，正在进行的前额叶皮层发育可以通过辨别逆向学习来评估，这是一项依赖于额叶纹状体完整性的任务。该任务也可能表明成年期mAMPH取样的易感性增加。
本研究的目的是调查青春期递增性mAMPH暴露对逆向学习（一项依赖前额叶皮层的任务，实验1）以及成年期后期mAMPH取样可能性（实验2）的长期影响。
与之前对成年期接受治疗的大鼠的研究不同，我们的结果显示，青春期mAMPH暴露后出现了更普遍的学习损伤，包括视觉辨别能力减弱以及逆向学习能力受损。此外，我们发现青春期预先接触mAMPH的大鼠在成年期摄入的药物明显更多。mAMPH的摄入量与这种学习呈正相关。综上所述，这些发现表明，即使在青春期适度接触mAMPH也可能在成年期诱发一般学习损伤，以及对mAMPH作用的持久敏感性。
