Effects of social stress and clomipramine on emotional memory in mice

We have previously observed impairing effects of social defeat stress (CSDS) on inhibitory avoidance (IA) in mice. Given the similarity between changes produced by social stress in animals and symptoms of certain human psychopathologies such as depression and anxiety, the effects of the antidepressant clomipramine on IA impairment produced by CSDS were evaluated in the present study. Male CD1 mice were randomly assigned to the groups: non-stressed+saline, non-stressed+clomipramine, stressed+saline and stressed+clomipramine. Stressed animals were subjected to daily agonistic encounters (10 min) in the home cage of the aggressor over a 20-day period. Just before each encounter, non-stressed and stressed mice were injected i.p. with saline or clomipramine (10 mg/kg) according to their experimental condition. 24 hours after the last CSDS session, all the mice were tested in a step-through IA task. In the IA training phase, animals were punished by a shock to the paw when they entered the dark compartment of the apparatus. In the IA test phase (one week later) the same procedure took place, but without shock. Complementary measures were obtained by evaluating all the animals in an elevated plus maze (locomotor activity and emotionality) and on a hot plate (analgesia). IA learning was confirmed in all groups except the stressed+saline group, which was the only one that exhibited higher anxiety levels. No variations were observed in either locomotor activity or analgesia. In conclusion, CSDS induces anxiety and impairs emotional memory in mice; the negative effects of CSDS on memory appear to be attenuated by clomipramine, and these detrimental effects do not seem to be secondary to the effects of CSDS on locomotor activity, emotionality or pain sensitivity.