Long-term effects of controllability or the lack of it on coping abilities and stress resilience in the rat.

Findings suggest that stress-induced impaired learning and coping abilities may be attributed more to the psychological nature of the stressor, rather than its physical properties. It has been proposed that establishing controllability over stressors can ameliorate some of its effects on cognition and behavior. Gaining controllability was suggested to be associated with the development of stress resilience. Based on repeated exposure to the two-way shuttle avoidance task, we previously developed and validated a behavioral task that leads to a strict dissociation between gaining controllability (to the level that the associated fear is significantly reduced) and a fearful state of uncontrollability. Employing this protocol, we investigated here the impact of gaining or failing to gain emotional controllability on indices of anxiety and depression and on subsequent abilities to cope with positively or negatively reinforcing learning experiences. In agreement with previous studies, rats exposed to the uncontrollable protocol demonstrated high concentration of sera corticosterone, increased immobility, reduced duration of struggling in the forced swim test and impaired ability to acquire subsequent learning tasks. Achieving emotional controllability resulted in resilience to stress as was indicated by longer duration of struggling in the forced swim test, and enhanced learning abilities. Our prolonged training protocol, with the demonstrated ability of rats to gain emotional controllability, is proposed as a useful tool to study the neurobiological mechanisms of stress resilience.

ERK2 and CREB activation in the amygdala when an event is remembered as "Fearful" and not when it is remembered as "Instructive".

A training protocol was developed based on durable exposure to the two-way shuttle avoidance task, in which the conditioned stimulus (CS), which was fear evoking for both training conditions on the first day of training, becomes instructive at the end of training under controllable conditions but remains fear evoking under the uncontrollable conditions. The protocol was utilized to examine whether, depending on the training regime, the memory formed will result in a different level of involvement of the amygdala. Three groups of rats were tested: controllable, subjected to durable avoidance learning; uncontrollable, subjected to the same training schedule but with no control over the stressor; and naive. Two weeks later, after the introduction of a reminder cue, freezing response, defecation, and blood corticosterone (CORT) of the uncontrollable group were higher than in the controllable and naive groups, indicating that indeed, for this group, the CS remained fear evoking. Significantly higher than chance shuttling responses of the controllable group indicated that, for them, the CS became "instructive." Activation of ERK2 and CREB in the basolateral amygdala (BLA) was highest in the uncontrollable group compared with the controllable and naive groups. Overall, the results indicate that the training procedure succeeded in dissociating between the physical (electric shock) and the psychological (control) attributes of the experience. Also, our findings support the view that an emotionally charged reminder cue activates the amygdala but that, as a previously fear-evoking memory cue becomes instructive, the involvement of the amygdale lessens.

Enriched environment experience overcomes learning deficits and depressive-like behavior induced by juvenile stress.

Mood disorders affect the lives and functioning of millions each year. Epidemiological studies indicate that childhood trauma is predominantly associated with higher rates of both mood and anxiety disorders. Exposure of rats to stress during juvenility (JS) (27-29 days of age) has comparable effects and was suggested as a model of induced predisposition for these disorders. The importance of the environment in the regulation of brain, behavior and physiology has long been recognized in biological, social and medical sciences. Here, we studied the effects of JS on emotional and cognitive aspects of depressive-like behavior in adulthood, on Hypothalamic-Pituitary-Adrenal (HPA) axis reactivity and on the expression of cell adhesion molecule L1 (L1-CAM). Furthermore, we combined it with the examination of potential reversibility by enriched environment (EE) of JS - induced disturbances of emotional and cognitive aspects of behavior in adulthood. Three groups were tested: Juvenile Stress -subjected to Juvenile stress; Enriched Environment--subjected to Juvenile stress and then, from day 30 on to EE; and Naïves. In adulthood, coping and stress responses were examined using the elevated plus-maze, open field, novel setting exploration and two way shuttle avoidance learning. We found that, JS rats showed anxiety- and depressive-like behaviors in adulthood, altered HPA axis activity and altered L1-CAM expression. Increased expression of L1-CAM was evident among JS rats in the basolateral amygdala (BLA) and Thalamus (TL). Furthermore, we found that EE could reverse most of the effects of Juvenile stress, both at the behavioral, endocrine and at the biochemical levels. The interaction between JS and EE resulted in an increased expression of L1-CAM in dorsal cornu ammonis (CA) area 1 (dCA1).