Aging impairs the antidepressant-like response to citalopram in male rats

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 14 months, respectively) were exposed to a chronic mild stress schedule for 3 weeks. After this period, the animals that developed anhedonia, reflected as a reduction in sucrose solution (1%) intake, were treated with citalopram (10 mg/kg/day) during 21 days 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.