Anabolic Androgenic Steroids : Neurobiological Effects of Nandrolone, Testosterone, Trenbolone, and Stanozolol

Sammanfattning: The use of anabolic androgenic steroids (AAS) for recreational purposes is a health concern, as long-term AAS-use in supraphysiological doses is associated with severe physical and psychological adverse effects. Several behavioral and cognitive problems are reported after long-term AAS-use, and alterations in brain morphology as well as neurotransmitter systems have been reported. The AAS-induced negative impact on the brain may depend on the type of AAS used, but the rationale behind the adverse effects observed is still not clear.The aim of the present thesis was to investigate the neurobiological impact of supraphysiological doses of structurally diverse AAS; testosterone, nandrolone, stanozolol, and trenbolone, as well as of the prodrugs nandrolone decanoate, testosterone undecanoate, testosterone decanoate, and trenbolone decanoate. Wistar rats were used to study the influence on behavior, effects on the brain, and additional somatic effects. Furthermore, in vitro models of immature and mature primary rat cortical cell cultures were used to examine the potential toxic properties of the AAS administered. In the in vitro studies, nandrolone and trenbolone were identified as the most toxic of the AAS investigated, due to their adverse impact on mitochondrial function, membrane integrity, apoptosis, and neurite outgrowth. In vivo, the AAS demonstrated diverse somatic outcomes affecting body weight development, and organ weights to different degrees. In addition, nandrolone decanoate caused a reduced general activity, an effect possibly induced by increased stress vulnerability and alterations in the oxytocinergic system. Furthermore, nandrolone decanoate induced impaired memory in the novel object recognition test. Overall, nandrolone decanoate was identified as the most harmful steroid investigated due to its prominent impact on body weight development, affecting multiple organs, and being the only AAS causing impaired cognitive function. In conclusion, the structurally different AAS exerted diverse effects on cell viability, neurite development as well as regarding physical impairments and impact on behavior, suggesting that harmful physiological, neurological, and psychological outcomes may be expected after AAS-use. These findings highlight that the severity and type of adverse effects depend on the type of AAS used, which is valuable information to consider in order to provide good healthcare and treatment options to AAS-users.