Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina, 27157, USA.
Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina, 27157, USA.
Neuropharmacology. 2020 Sep 15;175:108163. doi: 10.1016/j.neuropharm.2020.108163. Epub 2020 May 29.
Adolescence is characterized by changes in behavior, such as increases in sensation seeking and risk taking, and increased vulnerability to developing a range of psychiatric disorders, including substance abuse disorders (SUD) and mood disorders. The mesolimbic dopamine system plays an essential role in mediating these behaviors and disorders. Therefore, it is imperative to understand how the dopamine system and its regulation are changing during this period of development. Here, we used ex vivo fast scan cyclic voltammetry to compare stimulated dopamine release and its local circuitry regulation between early adolescent and adult male and female Sprague-Dawley rats. We found that, compared to adults, adolescent males have decreased stimulated dopamine release in the NAc core, while adolescent females have increased dopamine release in the NAc shell, NAc core, and DMS. We also found sex- and region-specific differences in other dopamine dynamics, including maximal dopamine uptake (Vmax), release across a range of stimulation frequencies, and autoreceptor regulation of dopamine release. Better understanding how the dopamine system develops during adolescence will be imperative for understanding what mediates adolescent vulnerability to developing psychiatric disorders and how disruptions during this period of reorganization could alter behaviors and vulnerability into adulthood.
青春期的行为会发生变化,例如感觉寻求和冒险行为增加,以及更容易患上一系列精神障碍,包括物质使用障碍(SUD)和情绪障碍。中脑边缘多巴胺系统在调节这些行为和障碍方面起着至关重要的作用。因此,了解多巴胺系统及其调节在这一发育阶段如何变化至关重要。在这里,我们使用离体快速扫描循环伏安法比较了早期青春期和成年雄性和雌性 Sprague-Dawley 大鼠的伏隔核核心和壳中刺激多巴胺释放及其局部回路调节。我们发现,与成年人相比,青春期雄性大鼠的 NAc 核心中刺激多巴胺释放减少,而青春期雌性大鼠的 NAc 壳、NAc 核心和 DMS 中多巴胺释放增加。我们还发现其他多巴胺动力学存在性别和区域特异性差异,包括最大多巴胺摄取(Vmax)、在一系列刺激频率下的释放以及多巴胺释放的自身受体调节。更好地了解多巴胺系统在青春期的发育过程对于理解是什么导致青少年易患精神障碍以及这段重组期的中断如何改变成年后的行为和易感性至关重要。