The Role of Anabolic Androgenic Steroids in Disruption of the Physiological Function in Discrete Areas of the Central Nervous System

Abstract

Anabolic-androgenic steroids (AAS) abuse is often associated with a wide spectrum of adverse effects. These drugs are frequently abused by adolescents and athletes for esthetic purposes, as well as for improvement of their endurance and performances. In this literature review, we evaluated the correlation between AAS and anxiety or aggression. Two pathways are thought to be involved in AAS-induced behavioral disorders. Direct pathway via the amygdalo-fugal pathway, which connects the central nucleus of the amygdala to the brainstem, is involved in cognitive-emotive and homeostatic processes. The latter is modified by chronic AAS use, which subsequently leads to increased anxiety. Indirect pathways via the serotonergic, dopaminergic, and glutamatergic signals which are modified by AAS abuse in latero-anterior hypothalamus and can mediate the aggressive behavior. In conclusion, the molecular mechanisms underlying the behavioral alterations following AAS abuse is unclear and remains ambiguous as additional long-term studies aimed to understand the precise mechanisms are required.

Keywords: Abuse; Amygdala; Anabolic-androgenic steroids (AAS); Behavioral disorders; Central nervous system; Molecular mechanisms.

Fig. 1

Cerebral structure involved in AAS-induced damage and their connections. The pathway thought to determine AAS-induced behavioral disorders concerned the amygdalo-fugal signaling, which connects the central amygdala (CeA) to bed nucleus of the stria terminalis (BnST) involves supraoptic neurons (nSO) and affects latero-anterior hypothalamus (LAH)

Fig. 2

Chronic administration of high doses of anabolic-androgenic steroids (AAS) promote anxiety-like behavior, through corticotrophin release factor (CRF) by enhancing GABAergic inhibitory effects from central amygdala (CeA) onto bed nucleus of the stria terminalis (BnST). Moreover, chronic AAS administration alters neurotransmitter expression involved in aggression control. AAS enhanced D₂R-mediated activation from supraoptic neurons (nSO) onto latero-anterior hypothalamus (LAH) and blocked GABA-mediated inhibition of AVP cells. In addition, AAS promote inverse relationship between 5-HT_1A-R-induced inhibition and 5-HT_2A-R-induced excitation, modifying their expression in hypothalamus. Finally, AAS are able to induce NMDA receptor phosphorylation in order to increase excitatory neurotransmission, resulting in an increment of aggression

Fig. 3

AAS-mediated neurotransmitter release and their action on latero-anterior hypothalamus (LAH): two different arrows are used to indicate inhibitory and excitatory action on LAH. These pathways are useful to clarify the AAS action on human behavior