Repeated social defeat stress enhances the anxiogenic effect of bright light on operant reward-seeking behavior in rats

Abstract

Repeated stress can trigger episodes of depression, along with symptoms of anhedonia and anxiety. Although often modeled separately, anxiogenic factors potently modulate hedonic, or appetitive, behavior. While repeated stress can increase anxiety and decrease appetitive behavior, it is not clear whether repeated stress can influence the impact of anxiogenic factors on appetitive behavior. This study tests whether repeated stress shifts behavior in a task that measures anxiogenic-appetitive balance. To test this, adult male rats were trained to lever press for sucrose pellet reward, and the effect of anxiogenic bright light on this behavior was measured. The impact of the bright light anxiogenic stimulus on lever pressing was compared between groups exposed to either daily repeated social defeat stress or control handling. We found that repeated stress reduced exploration in the open field and decreased social interaction, but had minimal effect on baseline lever pressing for reward. Repeated stress substantially enhanced the effect of anxiogenic bright light on lever pressing. This effect was greater two days after the last stress exposure, and began to diminish within two weeks. These data demonstrate that the anxiogenic and anhedonic features induced by repeated stress can be separately measured, and that the impact of anxiogenic stimuli can be greatly enhanced after repeated stress, even in the face of appetitive drive. The data also demonstrate that some apparent anhedonic-like effects of repeated stress can be due to increased sensitivity to anxiogenic stimuli, and may reflect an imbalance in an appetitive approach-withdrawal continuum.

Keywords: Anxiety; Appetitive; Light; Repeated stress; Social defeat; Sucrose.

Figure 1. Repeated social defeat increases anxiety-like behavior

A) Schematic of the experimental timeline. One day after completion of appetitive training, rats were subjected to daily social defeat or control procedures for 5 consecutive days. Beginning after 2 days or 2 weeks, rat behavior was measured in the open field test (OF), social interaction test (SI), and appetitive test (AppT). B) Rats that were exposed to social defeat displayed decreased exploration in the center of the open field when measured at 2 days but not 2 weeks (left), with no significant difference in total distance traveled (right). C) While there was no significant effect of social defeat on the number of social interactions (left), there was a significant decrease in the total time of social interaction (middle) and the duration of social contacts (right). * p<0.05 in post hoc Holm-Sidak after two-way ANOVA.

Figure 2. Repeated social defeat does not impact appetitive lever-pressing

A) Rats were trained in an appetitive conditioning task to lever press for sucrose, were matched for lever-pressing and then randomly assigned to control or stress groups. Indicative of the effectiveness of the matching, there was no significant difference between these groups in the number of active or inactive lever presses before control or stress procedures. B) Presentation of a bright light suppressed lever-pressing in the control group, compared to the no-light condition. The total number of active lever presses during the three 5-minute segments of appetitive testing was not significantly different (right). C) In a separate group of rats, there was no significant difference in lever-pressing between control and stress groups on the number of active lever presses in 5-minute segments (Testing phase) when measured after control or stress procedures (left). There was no significant difference between control and stress groups in the total number of active lever presses of the three 5-minute segments of appetitive testing (right).

Figure 3. Repeated social defeat increases the effect of anxiogenic bright light on appetitive lever-pressing

Rats were exposed to a testing session with 5-minute offon- off segments of bright light. A) Bright light presented during appetitive testing suppressed lever pressing when tested after 2 days. The effect of bright light was greater in rats that were exposed to repeated stress and this effect lasted longer than the duration of the light (left, *p<0.05 in post hoc Holm-Sidak after two-way ANOVA). This led to a decrease in the total number of active lever presses during this appetitive testing session in rats that were exposed to repeated stress (right). B) Bright light presented during appetitive testing suppressed lever pressing when tested after 2 weeks. The effect of bright light was greater in rats that were exposed to repeated stress, but did not last longer than the duration of the light (left, *p<0.05 in post hoc Holm-Sidak after two-way ANOVA). There was no significant difference in the total number of active lever presses during this appetitive testing session between control and stress groups (right). C) To directly compare the effects of stress when tested after 2 days or 2 weeks, the effect of bright light was subtracted from baseline (see Methods, 2.7 Data Acquisition and Analysis) and compared across time. Stress significantly enhanced the effect of anxiogenic light on active lever pressing (left), and this effect was greater when measured after 2 days compared to 2 weeks.