The immediate effects of AAS in the brain are mediated by their binding to androgen (male sex hormone) and estrogen (female sex hormone) receptors on the surface of a cell. This AAS–receptor complex can then shuttle into the cell nucleus to influence patterns of gene expression. Because of this, the acute effects of AAS in the brain are substantially different from those of other drugs of abuse. The most important difference is that AAS are not euphorigenic, meaning they do not trigger rapid increases in the neurotransmitter dopamine , which is responsible for the “high” that often drives substance abuse behaviors. However, long-term use of AAS can eventually have an impact on some of the same brain pathways and chemicals—such as dopamine, serotonin, and opioid systems—that are affected by other drugs of abuse. Considering the combined effect of their complex direct and indirect actions, it is not surprising that AAS can affect mood and behavior in significant ways.
Neural injections of Bromodeoxyuridine (BrdU) were applied to males of both groups to test for neurogenesis . Analysis showed that testosterone and dihydrotestosterone regulated adult hippocampal neurogenesis (AHN). Adult hippocampal neurogenesis was regulated through the androgen receptor in the wild-type male rats, but not in the TMF male rats. To further test the role of activated androgen receptors on AHN, flutamide , an antiandrogen drug that competes with testosterone and dihydrotestosterone for androgen receptors , and dihydrotestosterone were administered to normal male rats. Dihydrotestosterone increased the number of BrdU cells, while flutamide inhibited these cells.