The illicit use of anabolic androgenic steroids (AAS) has gained popularity among adolescents in the last decade. However, although it is known that exposure to AAS impairs cognition in adult animal models, the cognitive effects during adolescence remain undetermined. An inhibitory avoidance task (IAT) was used to assess the effect of AAS (17α-methyltestosterone; 17α-meT-7.5 mg/kg) in male and female periadolescent rats. A single injection of 17α-meT immediately before the footshock produced significant impairment of inhibitory avoidance learning in males but not females. Generalized anxiety, locomotion, and risk assessment behaviors (RAB) were not affected. Our results show that exposure to a single pharmacological dose of 17α-meT during periadolescence exerts sex-specific cognitive effects without affecting anxiety. Thus, disruption of the hormonal milieu during this early developmental period might have negative impact on learning and memory.

The abuse of anabolic steroids has increased at alarming rates among adolescents, however, little is known about their behavioral consequences in this population. Given that neuropeptide Y (NPY) and the androgen receptor (AR) are highly expressed in the hypothalamus, we aimed to assess the effects of 17a‐methyltestosterone (17a‐meT) in the behavioral and molecular aspects of the NPYergic circuit in this brain region. Male pubertal rats were chronically exposed to 17a‐meT. Animals were sacrificed and brain punches were done at the mPOA, VMN, and the extra‐hypothalamic BNST. NPY protein levels and mRNA expression for NPY and its receptors were determined by RIA and Real Time‐PCR, respectively. An increase in NPY was observed in the VMN, a region associated with male sexual motivation, while no changes were observed in the mPOA. Preliminary results showed a 3‐fold increase of NPY mRNA in the mPOA in AAS‐treated rats, and an 8‐fold decrease in the VMN. This effect was accompanied by a decrease in mRNA expression of receptors NPY Y2, Y5, and AR in the VMN. In the BNST, a 3‐fold decrease in NPY mRNA, and an increase in NPY Y1, Y2, and Y5 was observed. At the behavioral level, AAS‐treated rats increased the incentive sexual motivation. Our results suggest an interaction between synthetic androgens and neuropeptide systems to control behavior. NIH‐NCRR (2P20RR016470‐09), NIH‐EARDA (G11HD046326), RCMI (G12RR030551).

Anabolic androgenic steroids (AAS) are a class of steroid hormones derived from testosterone, being abused by adolescents, and known to affect anxiety, learning, and memory. The neural system underlying these behaviors includes the amygdala (AMY), a forebrain region that is known to express neuropeptide Y (NPY). NPY is one of the most abundant peptides in the brain and it plays a role in the regulation of energy homeostasis, anxiety and cognitive processes. Therefore, we aimed to assess NPY modulation in the AMY and in cognitive behavioral processes after chronic exposure to AAS in pubertal rats. Female and male pubertal rats were exposed to 17α‐methyltestosterone for two weeks. Food intake and body weight were measured during AAS exposure. For general anxiety and emotional memory, we used the Elevated Plus Maze (EPM) and the Passive Avoidance Task (PAT), respectively. Using RIA, we found a significant decrease in NPY levels in females, while there was no modulation in males. AAS in females showed an increase in body weight at the first and second weeks of AAS exposure, and an increase in food intake in the second week. In males, these differences were observed in the first, but not in the second week. Anxiety was not altered in male or female animals. Females but not males, showed a significant impairment of passive avoidance learning. Taken together, our results suggest that AAS can differentially modulate emotional memory and energy metabolism, maybe through NPY‐related neural circuits. Supported by RCMI (G12RR030551), NCRR‐NIH (P20RR016470).