Estudi dels efectes neuroplàstics i neurotòxics de l’MDMA en models experimentals d’alteracions del Sistema Nerviós Central

• Autores: Sònia Abad Florensa
• Directores de la Tesis: Elena Escubedo Rafa (dir. tes.), Jordi Camarasa (dir. tes.), Antoni Camins Espuny (dir. tes.)
• Lectura: En la Universitat de Barcelona ( España ) en 2016
• Idioma: catalán
• Tribunal Calificador de la Tesis: Coral Sanfeliu Pujol (presid.), Marta Barenys Espadaler (secret.), Francisco Javier Sureda Batlle (voc.)
• Materias:
  • Ciencias de la vida
    • Biología animal (zoología)
      • Comportamiento animal
    • Fisiología humana
      • Fisiología del sistema nervioso central
  • Psicología
    • Psicología experimental
      • Procesos de la memoria
    • Psicofarmacología
      • Abuso de drogas
• Enlaces
  • Tesis en acceso abierto en: Dipòsit Digital de la UB
• Resumen

  • MDMA is one of the most popular drugs used by young people and its consumption has been associated with many alterations in the brain. Hence, the study of the recreational use of this substance during adolescence is a matter of great interest. It has been established that its neurotoxicity is specie-selective. In humans, primates and rats it acts as a serotoninergic neurotoxin, while in mice it is mostly a dopaminergic one. In this work we focus on three main processes that could be affected by being exposed to MDMA. These processes are cognition process, seizures related to an excitotoxicty process and the effects of MDMA on a nigroestriatal pathway in a model of Familial Alzheimer’s Disease. The effects of MDMA on hippocampus plasticity and memory process depend on both the animal’s model and schedule of the treatment used. The administration of a chronic treatment of MDMA in adolescent rats produced an improved ability both in the learning of a new task and in the restrictive water maze, as well as an anxiolytic behavior. Changes in behavior and psychological functions are thought to be caused by the reorganization of synaptic connections. In our study, the MDMA treatment induced a decrease in spine density, which was reversed by training the rats in the water maze. In order to mimic the pattern of the consumption of the adolescents, a new treatment schedule was designed for mice. When memory process was assessed MDMA-exposed animals showed loss in a long-term memory even three month after finishing the treatment, probably related to a maladaptative plasticity triggered by a prolonged activation of IEGs. A recreational consumption of MDMA during adolescence enhances kainic acid convulsive susceptibility and potentiates kainate-induced neurodegeneration and astrogliosis, likely due to an ionic cellular disruption, in addition to the reduction of the expression of calcium binding proteins. Finally, we studied the effects of a recreational consumption of this amphetamine derivative during adolescence of APPswe/PS1dE9 mice, a model of familial Alzheimer’s disease. Our findings suggest that in this model MDMA anticipates the ulterior nigrostriatal dysfunction developed by these transgenic mice. Moreover, MDMA potentiates Aß deposition in the striatum.