Indomethacin counteracts the effects of chronic social defeat stress on emotional but not recognition memory in mice.

Abstract

We have previously observed the impairing effects of chronic social defeat stress (CSDS) on emotional memory in mice. Given the relation between stress and inflammatory processes, we sought to study the effectiveness of the anti-inflammatory indomethacin in reversing the detrimental effects of CSDS on emotional memory in mice. The effects of CSDS and indomethacin on recognition memory were also evaluated. Male CD1 mice were randomly divided into four groups: non-stressed + saline (NS+SAL); non-stressed + indomethacin (NS+IND); stressed + saline (S+SAL); and stressed + indomethacin (S+IND). Stressed animals were exposed to a daily 10 min agonistic confrontation (CSDS) for 20 days. All subjects were treated daily with saline or indomethacin (10 mg/kg, i.p.). 24 h after the CSDS period, all the mice were evaluated in a social interaction test to distinguish between those that were resilient or susceptible to social stress. All subjects (n = 10-12 per group) were then evaluated in inhibitory avoidance (IA), novel object recognition (NOR), elevated plus maze and hot plate tests. As in control animals (NS+SAL group), IA learning was observed in the resilient groups, as well as in the susceptible mice treated with indomethacin (S+IND group). Recognition memory was observed in the non-stressed and the resilient mice, but not in the susceptible animals. Also, stressed mice exhibited higher anxiety levels. No significant differences were observed in locomotor activity or analgesia. In conclusion, CSDS induces anxiety in post-pubertal mice and impairs emotional and recognition memory in the susceptible subjects. The effects of CSDS on emotional memory, but not on recognition memory and anxiety, are reversed by indomethacin. Moreover, memory impairment is not secondary to the effects of CSDS on locomotor activity, emotionality or pain sensitivity.