Anabolic androgenic steroids induce distinct monoaminergic and lipidomic alterations in the male rat brain

The illicit use of anabolic androgenic steroids (AAS) to enhance physical strength, performance, and appearance is associated with severe physical and psychological adverse effects. Long-term AAS use has been associated with altered behavior and cognitive impairments. Nevertheless, the neurobiological effects of AAS use remain underexplored, especially in terms of brain neurotransmitter and lipid profiles. This study applied advanced Fourier-transform ion cyclotron resonance matrix-assisted laser desorption/ionization mass spectrometry imaging (FTICR-MALDI-MSI) to investigate the effects of three AAS decanoate prodrugs, nandrolone, testosterone, and trenbolone, on brain monoamine neurotransmitter systems and lipid composition in male rats (n = 32). The AAS administration was found to alter dopamine and serotonin levels, as well as the metabolism of these molecules across multiple brain regions; significant effects on neurotransmitter levels, associated metabolites, and turnover ratios were observed. Additionally, AAS treatment affected brain lipid composition, with nandrolone and testosterone increasing the levels of phosphatidylethanolamines, ether-linked phosphatidylethanolamines, and phosphatidylserines; in contrast, trenbolone demonstrated an opposite trend. The presented findings revealed distinct, steroid-specific alterations in brain neurotransmitters and lipid profiles; these changes were particularly strong in the tail of the striatum, where lipid dysregulation was linked to neurotransmitter dynamics. The potential neurotoxic effects further highlight the importance of understanding how steroid-specific mechanisms are linked to behavioral and neurobiological changes. This study advances our knowledge of the neurobiological effects, including the potential risks, of extended AAS use.