Stress and cytokine effects on learning: What does sex have to do with it?

Abstract

Many studies have alluded to sexually dimorphic changes in behavior following stress. Although many have suggested that these changes are a function of stress-induced changes in learning and memory, there are questions regarding whether performance in those learning and memory tasks are influenced by stress-induced changes in drive more than in actual learning and memory processes. We used the classically conditioned eyeblink response (CCER) to determine whether slowed learning following stress in females can be explained by changes in unconditional response (UR) amplitude, a sign of a stress-induced shift in sensory reactivity. In addition, we had a second treatment group injected with the pro-inflammatory cytokine IL-1β to serve as an interoceptive stress condition, a physiological stressor with minimal stimulation to the animal. Replicating the work by Shors and colleagues, we found that stressed female rats had slower acquisition of the conditioned response (CR), but we also found that an IL-1β injection leads to a slowing of CR acquisition. However, in both cases, UR amplitude was lower in the treatment groups. We followed up these results by testing sensory reactivity through the acoustic startle response (ASR), where the magnitude of the ASR was marginally, but nonsignificantly, reduced by the same dose regimen of IL-1β. Together, these experiments suggest that tailshock stress and immune signaling (IL-1β) reduce sensory reactivity and the saliency of the stimuli used in the CCER, leading to slower learning in female rats.