Effects of testosterone and estradiol on anxiety and depressive-like behavior via a non-genomic pathway

Abstract

Besides their known slow genomic effects, testosterone and estradiol have rapid effects in the brain. However, their impact on mood-related behavior is not clear. The aim of this study was to investigate the non-genomic pathway of testosterone and estradiol in the amygdala in relation to anxiety and depressive-like behavior. Sham-operated and gonadectomized male rats (GDX) supplemented with testosterone propionate, estradiol, or olive oil were used. Five minutes after administration, anxiety and depression-like behavior were tested. Estradiol increased anxiolytic behavior in the open-field test compared to the GDX group, but administration of testosterone had no significant effect. Besides, c-Fos expression in the medial nucleus of the amygdala significantly increased after testosterone treatment compared to the GDX group, while no significant difference was observed in the central and the basolateral nuclei of the amygdala in the testosterone-treated group compared to the GDX group. In conclusion, estradiol had an anxiolytic effect via a rapid pathway, but no rapid effect of testosterone on anxiety was found. Further studies elucidating whether the rapid effect is mediated by a non-genomic pathway are needed.

Acute gonadotropin-releasing hormone agonist treatment enhances extinction memory in male rats

“…This may be partially due to the fact that males lack the natural fluctuations in gonadal hormones that females experience. Numerous studies have suggested that T may have anxiolytic and neuroprotective properties similar to those that have been reported for estrogen (Carrier et al, 2015; Filova et al, 2015; Almehmadi et al, 2016). For instance, men with higher levels of T reported better quality of life measures than those with lower levels (Cohen et al, 2016).…”

Testosterone Administration Moderates Effect of Social Environment on Trust in Women Depending on Second-to-Fourth Digit Ratio

“…Given the four-hour time course of effects we apply and since these effects occur after testosterone levels are normalized for several hours29, genomic effects can be presumed. This might especially be the case with an androgen pathway38. However, after conversion to estradiol, non-genomic effects might be more likely.…”

No effect of testosterone on behavior in aged Wistar rats

“…It is, however, unclear whether this fact can explain the differences in the outcomes. Especially, as some studies on young rats showed no effect of acute testosterone administration on anxiety- and depression-like behavior as well [33]. …”

“…Gonadectomized animals subsequently display increased anxiety- [26, 27] and depression-like [28] behavior, impaired cognitive performance [29–31] and altered social behavior [32]. It was shown that these negative effects of GDX can be reversed by administration of testosterone [26–28, 30], although some studies reported different and conflicting results [33, 34]. …”