Buck Jordan M, Morris Alysse S, Weber Sydney J, Raber Jacob, Siegel Jessica A
Department of Psychology, The University of the South, 735 University Avenue, Sewanee, TN 37318, USA.
Department of Behavioral Neuroscience, Oregon Health & Science University, 8131 SW Sam Jackson Park Road, Portland, OR 97239, USA.
Behav Brain Res. 2017 Apr 14;323:78-85. doi: 10.1016/j.bbr.2017.01.010. Epub 2017 Jan 12.
The neurotoxic effects of methamphetamine (MA) exposure in the developing and adult brain can lead to behavioral alterations and cognitive deficits in adults. Previous increases in the rates of adolescent MA use necessitate that we understand the behavioral and cognitive effects of MA exposure during adolescence on the adolescent brain. Adolescents using MA exhibit high rates of nicotine (NIC) use, but the effects of concurrent MA and NIC in the adolescent brain have not been examined, and it is unknown if NIC mediates any of the effects of MA in the adolescent. In this study, the long-term effects of a neurotoxic dose of MA with or without NIC exposure during early adolescence (postnatal day 30-31) were examined later in adolescence (postnatal day 41-50) in male C57BL/6J mice. Effects on behavioral performance in the open field, Porsolt forced swim test, and conditioned place preference test, and cognitive performance in the novel object recognition test and Morris water maze were assessed. Additionally, the effects of MA and/or NIC on levels of microtubule associated-2 (MAP-2) protein in the nucleus accumbens and plasma corticosterone were examined. MA and NIC exposure during early adolescence separately decreased anxiety-like behavior in the open field test, which was not seen following co-administration of MA/NIC. There was no significant effect of early adolescent MA and/or NIC exposure on the intensity of MAP-2 immunoreactivity in the nucleus accumbens or on plasma corticosterone levels. These results show that early adolescent MA and NIC exposure separately decrease anxiety-like behavior in the open field, and that concurrent MA and NIC exposure does not induce the same behavioral change as either drug alone.
在发育中的大脑和成年大脑中,甲基苯丙胺(MA)暴露的神经毒性作用可导致成年人出现行为改变和认知缺陷。此前青少年使用MA的比率有所上升,这就要求我们了解青少年时期MA暴露对青少年大脑的行为和认知影响。使用MA的青少年同时使用尼古丁(NIC)的比率很高,但MA和NIC同时作用于青少年大脑的影响尚未得到研究,而且NIC是否介导MA对青少年的任何影响也尚不清楚。在本研究中,在雄性C57BL/6J小鼠青春期后期(出生后第41 - 50天),研究了青春期早期(出生后第30 - 31天)给予神经毒性剂量的MA伴或不伴NIC暴露的长期影响。评估了对旷场试验、波索尔特强迫游泳试验和条件性位置偏爱试验中行为表现的影响,以及对新物体识别试验和莫里斯水迷宫中认知表现的影响。此外,还研究了MA和/或NIC对伏隔核中微管相关蛋白2(MAP - 2)水平和血浆皮质酮的影响。青春期早期单独暴露于MA和NIC可分别降低旷场试验中的焦虑样行为,而MA/NIC联合给药后未出现这种情况。青春期早期暴露于MA和/或NIC对伏隔核中MAP - 2免疫反应强度或血浆皮质酮水平没有显著影响。这些结果表明,青春期早期单独暴露于MA和NIC可分别降低旷场试验中的焦虑样行为,并且MA和NIC同时暴露不会诱导与单独使用任何一种药物相同的行为变化。