Study of the neurobiological mechanisms involved in the development of eating and addictive disorders

• Autores: Miriam Gutiérrez Martos
• Directores de la Tesis: Rafael Maldonado López (dir. tes.), Miquel Martín Sánchez (codir. tes.)
• Lectura: En la Universitat Pompeu Fabra ( España ) en 2018
• Idioma: español
• Tribunal Calificador de la Tesis: Marta Torrens Melich (presid.), Fernando Fernández Aranda (secret.), Ana Dopazo González (voc.)
• Programa de doctorado: Programa de Doctorado en Biomedicina por la Universidad Pompeu Fabra
• Materias:
  • Psicología
    • Psicofarmacología
      • Tratamiento de la drogadicción
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• Resumen

  • Drug addiction and several eating disorders share striking similarities in their behavioural patterns triggered by the presence of neuronal alterations in the brain reward circuit. In this Thesis, we investigate the neurobiological mechanisms modulating the rewarding effects of a drug of abuse, cocaine, and the progression of some eating disorders. Firstly, we evaluated the effect of three natural isoflavones, daidzin, daidzein and genistein, and a reference compound, disulfiram, in the modulation of the reinforcing and relapsing properties of cocaine in mice. Among them, the natural isoflavone daidzein presents a promising therapeutic effect decreasing cocaine reinforcing effects and relapse that surpasses those of disulfiram. Other rewarding stimuli able to develop abnormal behavioural responses are highly palatable foods such as those rich in sugar and fat. Ad libitum exposure to cafeteria diet foments overeating and overweight in mice and leads to neuroplastic modifications in the brain reward system. We have now demonstrated for the first time that microglia reactivity and neuroinflammation are responsible of the neurobiological adaptations observed in this model of free-choice diet that resembles the human food availability environment. Moreover, we also set-up and validated an operant animal model of high palatable food-induced addictive-like behaviour in mice applying the same criteria to diagnose drug addiction in the DSM-5. We have revealed in this model epigenetic changes in the Cnr1 promoter induced by the chronic exposure to palatable food.