Effects of social stress on locus coeruleus activity and cognitive flexibility

Abstract

The locus coeruleus (LC)‐norepinephrine (NE) system has been implicated in hyperarousal, a core feature of stress‐related psychiatric disorders. Because chronic social stress (CSS) is a common stressor, we characterized the consequences of CSS on LC‐NE system using the resident‐intruder model. The goal of this study was to determine whether CSS alters LC neuronal activity and AST performance. Sprague Dawley rats were implanted with a multiwire bundle into the LC and baseline activity was recorded before day 1 and 7 of CSS. LC activity decreased after 5 days of CSS (Day 1: 2.04±0.05 Hz, Day 7: 1.26±0.06 Hz; n=25), but not in controls (CTRL; Day 1: 2.70±0.05 Hz, Day 7: 2.61±0.03 Hz, n=12). Additionally, after CSS LC neurons showed a slow oscillation (0.1Hz). Rats were then tested in AST after CSS and LC activity was recorded. CSS rats performed better in intradimensional set shifting (IDS): 36.7±4 and 23.8±4 trials to criterion for CTRL (n=11) and CSS (n=10) respectively (p<0.05). Recordings during simple discrimination showed that CTRL LC activity (4.8±0.5Hz; 14 cells, 2 rats) were higher than CSS (3.2±0.3Hz; 27 cells, 3 rats) throughout the task (p<0.05). A repeated measures ANOVA revealed an effect of group, an effect of time and a group by time interaction (p<0.005). Together, the data suggest that CSS may improve the formation of set and that CSS alters the rate and pattern of LC neuronal activity. DARPA grant‐58077 LSDRP.