Fig. 1.
Lactate mediates resilience to chronic social defeat stress and rescues social avoidance behavior and anxiety. a The chronic social defeat paradigm consists of 10 days of daily defeat sessions that involve direct physical contact with an aggressor mouse for 7 min. On the 11th day, behavioral tests and tissue collection are conducted. Mice receive daily intra-peritoneal injections of either vehicle, lactate or the class I HDAC inhibitor, CI-994, 4 h before each defeat session. b Lactate increases resilience to stress. In the group of mice (n = 33) receiving saline and subjected to CSDS 24.2% are resilient to stress, whereas 75.8% are susceptible to stress. In the group of mice (n = 32) receiving lactate (180 mg/kg, daily for 10 days) and subjected to CSDS, 71.9% are resilient to stress, whereas 28.1% are susceptible to stress. c Intra-peritoneal injections of lactate (180 mg/kg, daily for ten days) reverse the chronic social defeat phenotype as shown by the increase in the time spent in interaction zone of the social interaction test. Statistical significance was measured by two-way Anova followed by multiple comparison test. Significance was measured vs. the defeat groups (Interaction: treatment F1,85 = 31.17, p < 0.0001 and stress F1,85 = 17.77, p < 0.0001; No interaction: treatment F1,85 = 19.61, p < 0.0001 and stress F1,85 = 9.008, p = 0.0035). ****p < 0.0001. The n numbers for the control, control + lactate, defeat (susceptible), and defeat + lactate are 15, 16, 25, and 32 respectively. d Intra-peritoneal injections of lactate decrease anxiety as measured by the significant increase in the time spent in the open arms of the elevated plus maze (EPM). Statistical significance was measured by unpaired t-test. Significance was measured vs. the defeat groups *p < 0.05. The n numbers for the control, control + lactate, defeat (susceptible), and defeat + lactate are 15, 16, 25, and 32, respectively. e The locomotor activity of all mice groups was not affected by lactate or defeat as measured by the distance traveled in the open field. Statistical significance was measured by one-way Anova followed by the Tukey’s multiple comparison test (F3,54 = 1.162, p = 0.3328)