Testosterone prevents but not reverses anhedonia in middle-aged males and lacks an effect on stress vulnerability in young adults

Middle-aged male rats are more vulnerable than young adult ones to develop anhedonia when exposed to chronic mild stress (CMS). Clinical studies support the idea that in aged subjects the low testosterone (T) levels are related with their higher stress vulnerability and that this hormone possesses antidepressant-like actions. In this study we evaluated the role of gonadal hormones — mainly T — on the depressive-like behavior of middle-aged and young adult male rats submitted to CMS. In middle-aged rats we analyzed the effect of T restitution (at the levels of young adult animals) given 3 weeks before (experiment 1) or 3 weeks after (experiment 2) anhedonia development (indicated by a reduction in sucrose solution intake). T restitution before CMS effectively prevented anhedonia but failed to reverse it once installed. In young adult rats we studied if orchidectomy increased stress vulnerability and found that it failed to modify sucrose intake. These results indicate a stress-dependent differential effect of T in middle-aged rats an age differential role of gonadal hormones on the vulnerability to develop anhedonia. The results suggest that T is a resilience factor in middle-aged but not in young adult males.

► Age-dependent role of testosterone on depressive-like behavior of male rats.
► We examine anhedonia development or reversal in the chronic mild stress paradigm.
► Testosterone prevents but not reverses anhedonia in middle-aged rats.
► Orchidectomy lacks an effect on stress vulnerability of young adults.
► Adequate testosterone levels in aged males prevent negative effects of stress.