Search

Decreased spatial memory is common in aging populations and reduces their quality of life. Although its role is still controversial, low testosterone (T) may contribute to impaired cognition in aged men. This study aimed to identify the role of T in age-related deficiencies in spatial memory among male rats. Young adult (3 months old) and aged (21 months old) Wistar rats were assigned to independent groups: intact, orchidectomized, or orchidectomized + subcutaneous pellets of T propionate. The phases of spatial memory acquisition (4 daily trials/4 days) and spatial memory retention (1 trial/day, 3 and 12 days after acquisition) were evaluated using the Barnes maze. Compared with young adults, aged intact rats took longer to find the goal, made more mistakes, and showed only slight improvements in goal sector exploration across the acquisition period. The young orchidectomized rats showed no improvement in performance over the days during the acquisition phase. T treatment in hormonally deprived old rats produced a small improvement in goal sector exploration and number of errors during the acquisition phase. Meanwhile, in young adults, this treatment improved the goal sector searching in the retention phase (12 days after acquisition training). Our results suggested that age-related spatial memory deficits cannot be entirely explained by the decline in T levels; however, this androgen produced subtle and mild beneficial effects on spatial memory in young and old males. Taken together, our findings suggest age differences in the role of T on spatial memory in males.

It has been suggested that old depressed patients require longer antidepressant treatments than their young counterparts. The objective of this study was to establish if aging impairs the response to an antidepressant by using an animal model. For this purpose, young and middle-aged male Wistar rats (of around 4 and 14months, respectively) were exposed to a chronic mild stress schedule for 3weeks. After this period, the animals that developed anhedonia, reflected as a reduction in sucrose solution (1%) intake, were treated with citalopram (10mg/kg/day) during 21days while still maintained under the chronic mild stress schedule. Non-stressed animals were included as controls. In young rats citalopram reversed the reduction in sucrose consumption induced by chronic mild stress after one week of treatment, while in middle-aged animals a similar reversion occurred after three weeks. Citalopram did not importantly modify simple water intake in stressed animals or sucrose consumption in non-stressed rats of both ages. The results imply that young rats have a lower latency of onset to the antidepressant-like effect of citalopram than middle-aged animals. The lower sensitivity of middle-aged animals to citalopram could be underlied by their lower levels of gonadal hormones.

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.