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

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.

Androgen synthesis inhibition but not gonadectomy reduces persistence during strategy set-shifting and reversal learning in male rats

“…In humans, rodents and birds, T treatment reduces behavioural flexibility [1][2][3][4][5][6][7][8] . In these studies, T does not impair learning but rather promotes persistence of a learned strategy and impairs shifting to a novel more advantageous one 9 . The prefrontal cortex (PFC), including the mPFC and orbitofrontal cortex (OFC), is essential for behavioural flexibility 10 .…”

“…Our main objective was to determine whether inhibition of androgen synthesis or GDX increased behavioural flexibility. T reduces behavioural flexibility, however in most previous studies T levels were increased to supraphysiological levels 4,6,9 . For example, Wallin and Wood administered a high dose of T to intact male rats and found impairments in set shifting and reversal learning 4 .…”

Effect of Resistance Training and Tribulus Terrestris Consumption on Avoidance and Working Memory in Rats Exposed to Stanozolol

“…As a result, they reduced dopaminergic function and disrupted the androgen regeneration system. All of these events led to decreased neuronal flexibility and affected learning and memory [24]. In this regard, the results of the studies demonstrated that long-term use of AAS led to a decrease in the number of healthy cells in the cortex, cerebellum, and hippocampus [2].…”

“…In this regard, the results of the studies demonstrated that long-term use of AAS led to a decrease in the number of healthy cells in the cortex, cerebellum, and hippocampus [2]. The injections of 7.5 mg/kg testosterone for 14 days also impaired learning in rats, thereby increasing the rate of cognitive impairment [24]. However, the mechanism of exercise activity has been known to increase neurotrophins, reduce oxidative stress, improve vascular circulation, and increase neuronal plasticity in the central nervous system [25].…”

Testosterone Deficiency and Risk of Cognitive Disorders in Aging Males

“…However, other authors reported that, in castrated male rats, high androgen levels exacerbate ischemic damage [ 25 ]. Similarly, a more recent study showed that chronic high-dose T administration impairs cognitive flexibility in a rat animal model [ 26 ].…”