Anabolic-androgenic steroid abuse and cognitive impairment: Testosterone IMPAIRS biconditional task performance in male rats

合成代谢雄性激素类固醇滥用与认知障碍:睾酮会损害雄性大鼠的双条件反射任务表现

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Abstract

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(1,18) = 5.21, p < 0.05) and drug x cue agreement x response accuracy (F(1,18) = 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.

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