Papel de los circuitos cerebrales amígdalo-corticales en la respuesta a la novedad en ratas adolescentes

Abstract

Taste neophobia and its attenuation (AN) have proven to be of great value for studying the brain mechanisms involved in responding to novelty along development in animal models. The present knowledge on the emotional component of the response to flavour novelty and the familiarization process is nevertheless scarce. Moreover, the results have been contradictory depending on the procedures and tests applied. Regarding the underlying brain circuit, the available evidence in adult rats is based on microdialysis and c-Fos immunohistochemistry. Although the results point to the involvement of the basolateral amygdala (BLA) activity both in taste neophobia and AN, they are often inconsistent. Besides, adolescent rats exhibit delayed AN depending on taste palatability in accordance with the increased reactivity to potentially harmful stimuli described in this developmental stage. It has been proposed that maturational differences between BLA and the medial prefrontal cortex (mPFC) might play a role in this effect since adult rats exhibit increased mPFC activity during the initial AN process. There is no evidence, however, in adolescent rats. This doctoral thesis contains three experimental series aimed at applying a developmental approach to study the amygdalo-cortical interaction involved in flavour neophobia and AN. The first experimental series explored in male and female adult rats the emotional processes involved in flavour neophobia and AN using a cider vinegar solution. Both the taste reactivity test (TRT) and the microanalysis of the licking structure (MLS) were combined in addition to the assessment of the amount ingested. MLS results, but not TRT, yielded a sex effect on taste reactivity and they allowed us to extent previous findings supporting increased palatability during acid flavour familiarization. The second experimental series explored the BLA participation in the emotional processes involved in AN by assessing the metabolic activity of the area using quantification of the cytochrome oxidase levels. The results evidenced a selective increase of BLA enzymatic activity during the second flavour exposure. This supports BLA involvement in the flavour familiarization process. Finally, the third experimental series applied c-Fos immunohistochemistry in order to assess in adolescent rats the activity of the different mPFC subregions during taste neophobia and AN. Using a cider vinegar solution, adolescents showed reduced mPFC activity in comparison to adults during AN. This can be related to the fact that more flavour exposures are required for completing AN at this age than in adulthood. These findings support that the activity of mPFC contributes to accelerate the AN process. Taken together, the results included in this doctoral thesis, taking advantage of a developmental approach, provide new evidence on the contribution of the emotional processes to taste neophobia and its attenuation revealing the participation of a complex amygdalo-cortical circuit.