Modeling anxiety and schizophrenia-related symptoms in the roman rats: effects of neonatal stimulation on behavioral inhibition, attentional-cognitive processes and regional brain volume
- Autores: CRISTOBAL del Río Álamos
- Directores de la Tesis: Albert Fernández-Teruel (dir. tes.)
- Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2017
- Idioma: español
- Tribunal Calificador de la Tesis: Osvaldo Giorgi (presid.), Carles Soriano Mas (secret.), Mª Carmen Torres Bares (voc.)
- Programa de doctorado: Programa de Doctorado en Neurociencias por la Universidad Autónoma de Barcelona
- Materias:
- Enlaces
- Tesis en acceso abierto en: TESEO
- Resumen
The present Doctoral Thesis reports a series of studies dealing with the effects of neonatal handling (NH) treatment on anxiety/stress and attentional-cognitive processes. All the studies were performed using the inbred Roman rat strains, which have been bi-directionally selected by their very good (RHA) vs extremely poor (RLA) acquisition of the two-way active avoidance response in the shuttle-box task. RLA rats are more anxious/fearful than their hypoemotional RHA counterparts, which in turn display higher impulsivity and worse attentional/cognitive performance than the former. Our work was aimed to address two main objectives: First, to evaluate the potential NH-improving effects on both, the anxiety/stress and attentional/cognitive profiles of both strains of rats. Secondly, to evaluate regional volumetric differences (using structural MRI) between both rat strains in brain areas related to anxiety, stress and cognition, as well as the eventual long-lasting effects of NH on anxiety- and attention/cognition-related brain regions. To this aim, three studies were conducted: Study 1 and Study 2 were mainly focused on anxiety/stress responses. Thus, we evaluated the effects of NH on anxiety/fear phenotypes, on post-stress hormonal responses and on the volume of specific brain areas involved in anxiety/stress processes (e.g. hippocampus, amygdala). Study 3 was aimed at evaluating some attentional/cognitive processes in RHA and RLA rats, as well as the potential NH effects on sensorimotor gating (prepulse inhibition, PPI) and executive functions (spatial learning/memory and working memory) in both rat strains. The volume of relevant brain areas (medial prefrontal cortex, anterior cingulate, nucleus accumbens, lateral ventricles) was also measured through MRI. Our results showed that: i) NH reduced anxiety and stress hormone responses in both strains of rats, with some effects being more marked in RLA rats, whereas NH also improved PPI and working memory in RHA rats; (ii) compared with their RHA counterparts, RLA rats showed enlarged amygdala, hippocampus and medial prefrontal cortex, and a dramatic reduction in the volume of the lateral ventricles; iii) NH induced a global reduction of amygdala volume in both strains, and also reduced hippocampus volume in RLA rats. In conclusion, NH induced improving effects on both strains of rats (anti-anxiety/stress effect in the RLA strain, and improvement of PPI and working memory in RHA rats). On the basis of PPI, cognitive and brain volumetric measures, it is proposed that the RHA rat strain could be a useful tool for the study of, at least some, relevant symptoms or neurobiological features relevant to schizophrenia.
