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Anabolic-androgenic steroids (AAS) are partly misused by males in order to become brave and intoxicated and these agents are highly associated with psychosis, disinhibition, aggression and acts of violence. Since such behavioral states have been related to an imbalanced serotonergic system and the involvement of the serotonergic 5HT1B and the 5HT2 receptors, it was important to discern the impact of AAS on these receptors. The objective of our study was to investigate the effects of 2 weeks of treatment with the AAS nandrolone decanoate at three different doses (1, 5, 15 mg/kg/day) on the total specific binding of the radioligands [125I]-(±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (5HT2 receptors) by autoradiography. All doses caused a significant down-regulation of the 5HT1B receptor density in the hippocampal CA1 and in the medial globus pallidus and a significant up-regulation of the 5HT2 receptor density in the nucleus accumbens shell. Alterations in receptor density were also observed in the lateral globus pallidus, ventromedial hypothalamus, the amygdala and in the intermediate layers of various cortex regions. In conclusion, serotonergic 5HT1B or 5HT2 receptors are likely to play important roles in mediating observed emotional states and behavioral changes among AAS abusers. [Copyright &y& Elsevier]

The use of anabolic androgenic steroids (AASs) among non-athletes is a public health-problem, as abusers underestimate the negative effects associated with these drugs. The present study investigated the toxic effects of testosterone, nandrolone, stanozolol, and trenbolone, and aimed to understand how AAS abuse affects the brain. Mixed cortical cultures from embryonic rats were grown in vitro for 7 days and thereafter treated with increasing concentrations of AASs for 24 h (single-dose) or 3 days (repeated exposure). Cells were co-treated with the androgen-receptor (AR) antagonist flutamide, to determine whether the potential adverse effects observed were mediated by the AR. Cellular toxicity was determined by measuring mitochondrial activity, lactate dehydrogenase (LDH) release, and caspase-3/7 activity. Nandrolone, unlike the other AASs studied, indicated an effect on mitochondrial activity after 24 h. Furthermore, single-dose exposure with testosterone, nandrolone and trenbolone increased LDH release, while no effect was detected with stanozolol. However, all of the four steroids negatively affected mitochondrial function and resulted in LDH release after repeated exposure. Testosterone, nandrolone, and trenbolone caused their toxic effects by induction of apoptosis, unlike stanozolol that seemed to induce necrosis. Flutamide almost completely prevented AAS-induced toxicity by maintaining mitochondrial function, cellular integrity, and inhibition of apoptosis. Overall, we found that supra-physiological concentrations of AASs induce cell death in mixed primary cortical cultures, but to different extents, and possibly through various mechanisms. The data presented herein suggest that the molecular interactions of the AASs with the AR are primarily responsible for the toxic outcomes observed., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Human growth hormone (GH) displays promising protective effects in the central nervous system after damage caused by various insults. Current evidence suggests that these effects may involve N-methyl-d-aspartate (NMDA) receptor function, a receptor that also is believed to play a role in opioid-induced neurotoxicity. The aims of the present study were to examine the acute toxic effects of methadone, an opioid receptor agonist and NMDA receptor antagonist, as well as to evaluate the protective properties of recombinant human GH (rhGH) on methadone-induced toxicity. Primary cortical cell cultures from embryonic day 17 rats were grown for 7days in vitro. Cells were treated with methadone for 24h and the 50% lethal dose was calculated and later used for protection studies with rhGH. Cellular toxicity was determined by measuring mitochondrial activity, lactate dehydrogenase release, and caspase activation. Furthermore, the mRNA expression levels of NMDA receptor subunits were investigated following methadone and rhGH treatment using quantitative PCR (qPCR) analysis. A significant protective effect was observed with rhGH treatment on methadone-induced mitochondrial dysfunction and in methadone-induced LDH release. Furthermore, methadone significantly increased caspase-3 and -7 activation but rhGH was unable to inhibit this effect. The mRNA expression of the NMDA receptor subunit GluN1, GluN2a, and GluN2b increased following methadone treatment, as assessed by qPCR, and rhGH treatment effectively normalized this expression to control levels. We have demonstrated that rhGH can rescue cells from methadone-induced toxicity by maintaining mitochondrial function, cellular integrity, and NMDA receptor complex expression., (Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.)