Characterization of resilience to the behavioural effects of social stress on female mice and its potentiation in both sexes
- Autores: Maria De Los Angeles Martinez Caballero
- Directores de la Tesis: María Asunción Aguilar Calpe (dir. tes.), María Carmen Arenas Fenollar (codir. tes.), María Pilar García Pardo (codir. tes.)
- Lectura: En la Universitat de València ( España ) en 2025
- Idioma: inglés
- Número de páginas: 335
- Tribunal Calificador de la Tesis: María Salud García Gutiérrez (presid.), Bruno Ribeiro do Couto (secret.), Stephanie Caille Garnier (voc.)
- Programa de doctorado: Programa Oficial de Doctorado en Investigación en Psicología
- Materias:
- Enlaces
- Resumen
Constant exposure to stressful stimuli can alter various areas of the brain, facilitating the development of mental disorders, cognitive deficits, and substance use disorders. In preclinical studies conducted in our laboratory, we have observed that exposure to social stress during adolescence, using the Intermittent Social Defeat (ISD) protocol, induces short-term negative effects, as well as an increase in the reinforcing effects of cocaine in the long term in the place preference conditioning (CPP) paradigm in male mice. However, not all stressed mice show CPL after exposure to ISD; that is, some are resilient to stress. These resilient animals are characterised by an active coping response to stress during episodes of defeat, greater concern about possible danger in the environment, and absence of depressive symptoms after exposure to stress during early or late adolescence. Furthermore, showing lower reactivity in a situation of moderate unavoidable stress also predicts resilience in mice stressed during late adolescence. Studies on social stress and resilience to its effects on drug use have been conducted mainly in males, despite the fact that the prevalence of stress-related disorders is higher in females. Studying sex differences in resilience and vulnerability to stress is essential for the development of sex-specific treatments for stress-related mental disorders. Therefore, the first general aim of this thesis is to determine the behavioural and cognitive effects that social stress induces in the short term and its long-term effects on the reinforcing properties of cocaine, as well as to characterise the behavioural traits associated with resilience to the effects of social stress on cocaine-induced CPP in female mice. The developmental timing of stress exposure is also an important variable to consider. Along these lines, we conducted a study in which females were exposed to social stress using the intermittent social defeat (ISD) and vicarious intermittent social defeat (VISD) protocol during late adolescence or the VISD protocol during early adolescence. The second general aim is to evaluate whether an environmental strategy, exposure to physical exercise, is effective in enhancing resilience to the negative effects of the VISD protocol in female mice. Finally, the third general aim is to evaluate the effectiveness of various pharmacological treatments in increasing resilience to the potentiation of cocaine CPP induced by exposure to social stress using the ISD protocol in male mice. In conclusion, this study makes important contributions to our understanding of the effects of exposure to social stress in female mice during early and late adolescence, as well as the behavioural characteristics associated with resilience and its enhancement through physical activity. It has also contributed to expanding knowledge of the neurobiological mechanisms underlying the behavioural effects of social stress in male mice and has identified possible pharmacological treatments (CBD, 7-nitroindazole, ketamine) to enhance resilience to the short- and long-term effects of exposure to social stress. In the future, it would be important to conduct studies to evaluate the efficacy of these treatments in female mice, in order to contribute to the development of sex-specific treatments for stress-related mental disorders.
