Department of Integrative Anatomical Sciences, Keck School of Medicine at the University of Southern California, Los Angeles, CA, 90033, United States.
Department of Integrative Anatomical Sciences, Keck School of Medicine at the University of Southern California, Los Angeles, CA, 90033, United States.
Behav Brain Res. 2020 Feb 3;379:112339. doi: 10.1016/j.bbr.2019.112339. Epub 2019 Nov 4.
Our goal is to understand the consequences of anabolic-androgenic steroid (AAS) abuse on cognitive function, using rats as a model. There is relatively little research on how AAS abuse impacts cognition. In the present study, rats were tested for their ability to use contextual information to guide decision-making in biconditional discrimination. The Stroop task is a classic human test for contextual decision-making. In rodents, biconditional discrimination challenges subjects to use contextual cues in the operant chamber to resolve the correct lever response when auditory and visual cues are incongruent. The hypothesis is that chronic high-dose testosterone impairs biconditional discrimination. Rats were trained in 24 trials/day over 14 days, in alternating sessions with each environment. On a flat floor with houselight illuminated, auditory cues (clicker vs tone) signified the active lever. On a barred floor with no light, visual cues from 2 stimulus lights (constant vs blinking) identified the active lever. Rats treated chronically with testosterone (7.5 mg/kg) were unimpaired in task acquisition, and all rats learned to select the correct lever in response to auditory or visual cues. During extinction, controls made significantly more correct than incorrect responses in congruent trials (p < 0.05 by paired t-test), but testosterone-treated rats failed to show a similar preference. This was reflected by significant interactions of drug x cue agreement (F = 5.21, p < 0.05) and drug x cue agreement x response accuracy (F = 8.95, p < 0.05). These results suggest that testosterone impairs cognitive flexibility, and demonstrates potential for AAS abuse to impair cognitive function in humans.
我们的目标是了解合成代谢雄激素类固醇（AAS）滥用对认知功能的影响，以大鼠为模型。关于 AAS 滥用如何影响认知，相关研究相对较少。在本研究中，我们通过大鼠双条件辨别任务来测试其利用环境信息进行决策的能力。Stroop 任务是一种经典的人类环境决策测试。在啮齿动物中，双条件辨别任务要求动物在操作箱中使用环境线索来解决听觉和视觉线索不一致时的正确杠杆反应。我们假设慢性大剂量睾酮会损害双条件辨别。大鼠在 14 天内每天接受 24 次训练，每天在两种环境中交替进行。在一个有灯光的平坦地板上，听觉线索（点击器与音调）代表活动杠杆。在一个没有灯光的带栏地板上，来自两个刺激灯（恒定光与闪烁光）的视觉线索代表活动杠杆。接受慢性睾酮（7.5mg/kg）治疗的大鼠在任务获取方面没有受到损害，所有大鼠都学会了根据听觉或视觉线索选择正确的杠杆。在消退阶段，对照组在一致的试验中做出的正确反应明显多于错误反应（配对 t 检验，p<0.05），而接受睾酮治疗的大鼠则没有表现出类似的偏好。这反映在药物 x 线索一致性（F=5.21，p<0.05）和药物 x 线索一致性 x 反应准确性（F=8.95，p<0.05）的显著交互作用上。这些结果表明，睾酮损害了认知灵活性，并表明 AAS 滥用有可能损害人类的认知功能。
