Study of molecular targets and neurobiologial mechanisms involved in compulsive overeating

Binge-eating disorder (BED) is a chronic eating disturbance that affects 1.6-2.0% of people worldwide. It is characterised by recurrent episodes of consuming large amounts of food in a short period, together with a sense of loss of control without using compensatory measures. This disorder is associated with significant psychiatric comorbidity and other eating disturbances like obesity and food addiction. Thus, BED is a complex multifactorial disorder whose neurobiological mechanisms involved are still unknown. The present Thesis characterised the involvement of a specific neuronal subpopulation in the nucleus accumbens expressing the dopamine receptor type-2 in binge-like eating, by comparing different dietary conditions and using a cell-specific transcriptomic approach. The bioinformatic analysis demonstrated similarities among different disorders, such as drug addiction and memory and learning task, which suggested that repetitive episodes of compulsive overeating may produce changes in dopamine signalling that differ from those occurring in obesogenic conditions. Specific pharmacological and adenoviral gene delivery approaches provided insights into understanding the neurobiological mechanisms involved in BED, which could help identify new pharmacological approaches to address this pathology. In addition, a well-characterised rodent model that recapitulates most of the symptoms described in psychiatric manuals for BED was proposed as a preclinical tool to explore the aetiological or susceptible factors to suffer this disorder in rodents without comparing to other eating disturbances. El trastorno por atracón (TA) es un desorden alimentario crónico que afecta al 1,6-2,0% de las personas en todo el mundo. Se caracteriza por episodios recurrentes de consumo de grandes cantidades de comida en un periodo corto, junto con una sensación de pérdida de control sin utilizar medidas compensatorias. Este trastorno se asocia a una importante comorbilidad psiquiátrica y a otras alteraciones alimentarias como la obesidad y la adicción a la comida. Así pues, el TA es un complejo trastorno multifactorial cuyos mecanismos neurobiológicos implicados son aún desconocidos. La presente Tesis caracterizó la participación de una subpoblación neuronal específica en el núcleo accumbens que expresa el receptor de dopamina tipo 2 en la regulación de la alimentación compulsiva, comparando diferentes condiciones dietéticas y utilizando un enfoque transcriptómico específico de tipo