Resumen de Resilience to social defeat-induced increased in ethanol intake: Neuroinflammation response
Social stress is the main risk factor for addictive behaviors. Stress-susceptible phenotypes have become in the last decade a target of study to enhance stress resilience. Promoting active coping through positive pharmacological and environmental interventions is scientifically validated in the treatment of addiction. However, these interventions to promote resilience during adolescence as a preventive measure have not been widely studied. Therefore, the main aim of the present Doctoral Thesis was to develop pharmacological and environmental strategies to enhance resilience to the negative effects induced by social defeat (SD) on behavior and the neuroinflammatory response.
To reach this aim, we first confirmed and characterized the neuroinflammatory potential of SD stress and its mediation of increased ethanol consumption. Subsequently, we assessed the potential of oxytocin administration or physical exercise to buffer the negative effects of SD on ethanol consumption and the neuroinflammatory response. After confirming that these interventions potentiate resilience to the deleterious effects of SD, we set out to characterize the preventive potential of exercise, environmental enrichment (EE) or stress inoculation during adolescence. These studies further characterized the vulnerability and resilience to SD experience during adolescence in mice, since the response to SD is complex and unique during this stage of life. Finally, a new line of research was initiated during an international research stay to further characterize these phenotypes, focusing on the study of neuronal and synaptic morphological changes and astrogliosis in key brain structures.
The results obtained in this Doctoral Thesis allow us to confirm that SD contributes to the development of social avoidance behaviors and increases long-term ethanol consumption through the activation of the immune system. We have confirmed the existence of distinct phenotypes based on SD-induced social avoidance behavioral responses, in both adult and adolescent mice. SD produces negative effects, but not in all exposed animals, since only a percentage of them develop a profile susceptible to depressive-type behaviors and increased alcohol consumption. Nonetheless, our main goal was to enhance the resilience response and we have shown that pharmacological interventions, such as oxytocin administration, or environmental interventions, can enhance the resilience response. These interventions can also be applied preventively during adolescence. For example, physical exercise, EE or social inoculation during adolescence induce a powerful resilient response. All these protective effects can be produced by various mechanisms; such as changes in BDNF or in neuronal architecture. However, the fundamental mechanism that appears to be common in resilient animals is a decrease in the neuroinflammatory response that is always observed to be increased in susceptible defeated animals.
