Contingency-based emotional resilience: effort-based reward training and flexible coping lead to adaptive responses to uncertainty in male rats

Abstract

Emotional resilience enhances an animal's ability to maintain physiological allostasis and adaptive responses in the midst of challenges ranging from cognitive uncertainty to chronic stress. In the current study, neurobiological factors related to strategic responses to uncertainty produced by prediction errors were investigated by initially profiling male rats as passive, active or flexible copers (n = 12 each group) and assigning to either a contingency-trained or non-contingency trained group. Animals were subsequently trained in a spatial learning task so that problem solving strategies in the final probe task, as well-various biomarkers of brain activation and plasticity in brain areas associated with cognition and emotional regulation, could be assessed. Additionally, fecal samples were collected to further determine markers of stress responsivity and emotional resilience. Results indicated that contingency-trained rats exhibited more adaptive responses in the probe trial (e.g., fewer interrupted grooming sequences and more targeted search strategies) than the noncontingent-trained rats; additionally, increased DHEA/CORT ratios were observed in the contingent-trained animals. Diminished activation of the habenula (i.e., fos-immunoreactivity) was correlated with resilience factors such as increased levels of DHEA metabolites during cognitive training. Of the three coping profiles, flexible copers exhibited enhanced neuroplasticity (i.e., increased dentate gyrus doublecortin-immunoreactivity) compared to the more consistently responding active and passive copers. Thus, in the current study, contingency training via effort-based reward (EBR) training, enhanced by a flexible coping style, provided neurobiological resilience and adaptive responses to prediction errors in the final probe trial. These findings have implications for psychiatric illnesses that are influenced by altered stress responses and decision-making abilities (e.g., depression).

Profiling coping strategies in male and female rats: Potential neurobehavioral markers of increased resilience to depressive symptoms

“…During the assessment, each animal was gently restrained on its back for 1 min so that the number of escape attempts (or wiggles) could be quantified (see Hawley et al, 2010; Lambert et al, 2014). Seven days later the same assessment was conducted; however, the animals were tested in a different order than the first assessment to avoid any confounding sequencing effects.…”

“…Thus, specific coping strategies may lead to emotional resilience by enhancing survival with minimal allostatic load (Yehuda et al, 2006; Lambert et al, 2014). Adding to the complexity of the stress response is the secretion of dehydroepiandrosterone (DHEA) which has been described as having anticorticosteroid effects in the brain (Feder et al, 2009).…”

“…When presented with a prediction error in a spatial task, for example, recent research suggests that contingency-trained animals exhibited more targeted search strategies than their noncontingent counterparts. Regardless of training, animals profiled as flexible copers exhibited enhanced evidence of neuroplasticity (i.e., doublecortin-immunoreactivity in the dentate gyrus), potentially associated with the cognitive training, when compared to their noncontingent-trained counterparts (Lambert et al, 2014). Disruptions of neuroplasticity, critical for neuronal adaptation in changing environmental landscapes, have been associated with the onset of mood disorders (Pittenger and Duman, 2008; Czeh and Simon, 2005).…”

“…Thus, when a prediction error is encountered, a network of various brain areas converge to facilitate the individual’s accurate assessment of the changing contingencies so that an alternative adaptive response is generated. This contingency-correcting network of brain areas necessary for flexible coping, working in the context of stress-modulating neurobiological factors such as amygdala and HPA activation, is likely critical in the determination of adaptive versus maladaptive responses in various stressful and threatening contexts (Yang et al, 2010; Lambert et al, 2014). …”

“…Rats profiled with a flexible coping phenotype, for example, exhibit increased neurobiological markers of emotional regulation compared to active and passive copers (Bardi et al, 2012; Lambert et al, 2014). In the current study, responses of male and female rats to prediction errors in a spatial foraging task (dry land maze; DLM) were examined after animals were exposed to chronic unpredictable stress (CUS).…”