Calma I Daphne, Persons Amanda L, Napier T Celeste
Departments of Psychiatry and Behavioral Sciences, Rush University Medical Center, Chicago, IL, 60612, USA.
Center for Compulsive Behavior and Addiction, Rush University Medical Center, Chicago, IL, 60612, USA.
Sci Rep. 2021 Dec 31;11(1):24529. doi: 10.1038/s41598-021-04301-9.
Repeated methamphetamine use leads to long lasting brain and behavioral changes in humans and laboratory rats. These changes have high energy requirements, implicating a role for mitochondria. We explored whether mitochondrial function underpins behaviors that occur in rats months after stopping methamphetamine self-administration. Accordingly, rats self-administered intravenous methamphetamine for 3 h/day for 14 days. The mitochondrial toxin rotenone was administered as (1 mg/kg/day for 6 days) via an osmotic minipump starting at 0, 14 or 28 days of abstinence abstinence. On abstinence day 61, expression of methamphetamine-induced behavioral sensitization was obtained with an acute methamphetamine challenge in rotenone-free rats. Rotenone impeded the expression of sensitization, with the most robust effects obtained with later abstinence exposure. These findings verified that self-titration of moderate methamphetamine doses results in behavioral (and thus brain) changes that can be revealed months after exposure termination, and that the meth-initiated processes progressed during abstinence so that longer abstinence periods were more susceptible to the consequences of exposure to a mitochondrial toxin.
反复使用甲基苯丙胺会导致人类和实验大鼠出现持久的大脑和行为变化。这些变化需要高能量支持，这表明线粒体发挥了作用。我们探究了线粒体功能是否是大鼠停止自我给药甲基苯丙胺数月后出现的行为的基础。因此，大鼠连续14天每天静脉自我给药甲基苯丙胺3小时。从禁欲0、14或28天开始，通过渗透微型泵给予线粒体毒素鱼藤酮（1毫克/千克/天，持续6天）。在禁欲第61天，对未使用鱼藤酮的大鼠进行急性甲基苯丙胺激发，以观察甲基苯丙胺诱导的行为敏化的表达情况。鱼藤酮阻碍了敏化的表达，后期禁欲暴露时效果最为明显。这些发现证实，适度甲基苯丙胺剂量的自我滴定会导致行为（进而大脑）变化，这些变化在暴露终止数月后仍可显现，并且甲基苯丙胺引发的过程在禁欲期间持续发展，因此禁欲时间越长，越容易受到线粒体毒素暴露后果的影响。
