Behavioral Neuroscience Program, Department of Psychology, Northeastern University, Boston, MA 02155, USA.
Horm Behav. 2012 Nov;62(5):569-78. doi: 10.1016/j.yhbeh.2012.09.007. Epub 2012 Sep 28.
From the U.S. to Europe and Australia anabolic steroid abuse remains high in the adolescent population. This is concerning given that anabolic steroid use is associated with a higher incidence of pathological anxiety that often appears during withdrawal from use. This study uses pubertal Syrian hamsters (Mesocricetus auratus) to investigate the hypothesis that adolescent anabolic/androgenic steroid (AAS) exposure predisposes hamsters to heightened levels of anxiety during AAS withdrawal that is modulated by serotonin (5HT) neural signaling. In the first two sets of experiments, adolescent AAS-treated hamsters were tested for anxiety 21 days after the cessation of AAS administration (i.e., during AAS withdrawal) using the elevated plus maze (EPM), dark/light (DL), and seed finding (SF) tests and then examined for differences in 5HT afferent innervation to select areas of the brain important for anxiety. In the EPM and DL tests, adolescent AAS exposure leads to significant increases in anxiety-like response during AAS withdrawal. AAS-treated hamsters showed long-term reductions in 5HT innervation within several areas of the hamster brain implicated in anxiety, most notably the anterior hypothalamus and the central and medial amygdala. However, no differences in 5HT were found in other anxiety areas, e.g., frontal cortex and lateral septum. In the last experiment, adolescent AAS-treated hamsters were scored for anxiety on the 21st day of AAS withdrawal following the systemic administration of saline or one of three doses of fluoxetine, a selective serotonin reuptake inhibitor. Saline-treated hamsters showed high levels of AAS withdrawal-induced anxiety, while treatment with fluoxetine reduced AAS withdrawal-induced anxiety. These findings indicate that early AAS exposure has potent anxiogenic effects during AAS withdrawal that are modulated, in part, by 5HT signaling.
从美国到欧洲和澳大利亚，青少年人群中滥用合成代谢类固醇的情况仍然很高。这令人担忧，因为合成代谢类固醇的使用与更高的病理性焦虑发生率有关，这种焦虑通常出现在使用停止后。本研究使用青春期叙利亚仓鼠（Mesocricetus auratus）来验证以下假设：青春期合成代谢/雄激素类固醇（AAS）暴露会使仓鼠在 AAS 戒断期间更容易出现焦虑，而 5-羟色胺（5HT）神经信号会调节这种焦虑。在前两组实验中，使用高架十字迷宫（EPM）、明暗（DL）和种子寻找（SF）测试，在停止 AAS 给药后 21 天测试青春期 AAS 处理的仓鼠的焦虑，即 AAS 戒断期间，然后检查 5HT 传入神经支配到对焦虑重要的大脑特定区域的差异。在 EPM 和 DL 测试中，青春期 AAS 暴露会导致 AAS 戒断期间焦虑样反应显著增加。AAS 处理的仓鼠在几个与焦虑有关的仓鼠大脑区域中表现出长期的 5HT 支配减少，特别是在前下丘脑、中央和内侧杏仁核。然而，在其他焦虑区域，如额叶皮层和外侧隔室，没有发现 5HT 的差异。在最后一项实验中，在 AAS 戒断的第 21 天，对青春期 AAS 处理的仓鼠进行 AAS 戒断诱导焦虑的评分，方法是系统给予生理盐水或三种氟西汀剂量之一，氟西汀是一种选择性 5-羟色胺再摄取抑制剂。生理盐水处理的仓鼠表现出高水平的 AAS 戒断诱导的焦虑，而氟西汀治疗降低了 AAS 戒断诱导的焦虑。这些发现表明，早期 AAS 暴露在 AAS 戒断期间具有强烈的焦虑作用，部分受到 5HT 信号的调节。
