Publication: Dopamine signaling is essential in cognitive process and motor performance
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2016-05-11
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Universidad Complutense de Madrid
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Abstract
La dopamina es uno de los principales neurotransmisores del sistema nervioso central y desempeña un papel esencial en diferentes funciones: neuroendocrinas, motivacionales/emocionales y, especialmente, motoras y cognitivas. Las funciones de la dopamina están media-das en gran medida por la estimulación de sus principales receptores D1 (D1R) y D2 (D2R). En esta tesis hemos estudiado el papel que ambos receptores desempeñan en los procesos de apren-dizaje y memoria, así como la regulación que ejercen sobre las neuronas estriatales TH-immunoreactivas (TH-ir) y su posible implicación en la respuesta motora. Para abordar este proyecto hemos utilizado ratones knock-out para el receptor D1 (Drd1a-/-) y D2 (Drd2-/-) ya que no existen compuestos farmacológicos capaces de diferenciar eficazmente entre receptores dopaminérgicos de la misma familia. Además, para el estudio de las neuronas TH-ir realizamos lesiones con 6-OHDA a ratones que posteriormente recibieron un tratamiento crónico con L-DOPA, siendo este el mecanismo más eficaz para inducir la expresión de las neuronas TH-ir objeto de nuestro estudio. Para completar todo ello realizamos test conductuales que evalúan respuesta motora, como el test del cilindro, y diferentes tipos de aprendizaje y me-moria para los cuales utilizamos test específicos. Entre estos test se encuentran: los laberintos de Barnes y Morris para memoria espacial, evitación activa/pasiva y condicionamiento del mie-do para el aprendizaje asociativo, y el reconocimiento de objetos para la memoria de reconoci-miento...
Dopamine is one of the main neurotransmitters in the central nervous system involved in neuroendocrine, motivational/emotional and, especially, cognitive and motor functions. These processes are mediated by the stimulation of the principal dopamine receptors: D1 (D1R) and D2 (D2R). In this doctoral dissertation we studied the role of both receptors in learning and memory processes, as well as their regulation of striatal TH-immunoreactive (TH-ir) neurons and the involvement in motor response. To elaborate this project we used knock-out mice for D1 (Drd1a-/-) and D2 (Drd2-/-) receptors because there are no pharmacological agents that effectively differentiate between dopamine receptors of the same family. In addition, for the striatal TH-ir neurons study, we used mice with striatal unilateral 6-OHDA lesions, chronically treated with L-DOPA, this being the most effective mechanism to induce the expression of striatal TH-ir neurons. To complete this work, we carried out behavioral tests that analyze the motor response, e.g. cylinder test, and different types of learning and memory process, e.g. Barnes maze..
Dopamine is one of the main neurotransmitters in the central nervous system involved in neuroendocrine, motivational/emotional and, especially, cognitive and motor functions. These processes are mediated by the stimulation of the principal dopamine receptors: D1 (D1R) and D2 (D2R). In this doctoral dissertation we studied the role of both receptors in learning and memory processes, as well as their regulation of striatal TH-immunoreactive (TH-ir) neurons and the involvement in motor response. To elaborate this project we used knock-out mice for D1 (Drd1a-/-) and D2 (Drd2-/-) receptors because there are no pharmacological agents that effectively differentiate between dopamine receptors of the same family. In addition, for the striatal TH-ir neurons study, we used mice with striatal unilateral 6-OHDA lesions, chronically treated with L-DOPA, this being the most effective mechanism to induce the expression of striatal TH-ir neurons. To complete this work, we carried out behavioral tests that analyze the motor response, e.g. cylinder test, and different types of learning and memory process, e.g. Barnes maze..
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Psicología, Departamento de Psicobiología, leída el 22-10-2015