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Departament De Biologia Funcional DEPARTAMENT DE BIOLOGIA FUNCIONAL SISTEMAS DOPAMINÉRGICOS EN EL TELENCÉFALO DEL RATÓN: PAPEL EN EL PROCESAMIENTO DE ESTÍMULOS REFORZANTES NATURALES. JOSÉ MARTÍNEZ HERNÁNDEZ UNIVERSITAT DE VALÈNCIA Servei de Publicacions 2009 Aquesta Tesi Doctoral va ser presentada a València el dia 17 de juliol de 2009 davant un tribunal format per: - Dr. Agustín González Gallegos - Dr. Tomás González Hernández - Dr. Francisco Olucha Bordonau - Dra. Patricia Robledo Montoya - Dr. Juan Nácher Roselló Va ser dirigida per: Dr. Fernando Martínez García Dr. Enrique Lanuza Navarro ©Copyright: Servei de Publicacions José Martínez Hernández Dipòsit legal: V-946-2011 I.S.B.N.: 978-84-370-7713-0 Edita: Universitat de València Servei de Publicacions C/ Arts Gràfiques, 13 baix 46010 València Spain Telèfon:(0034)963864115 SISTEMAS DOPAMINÉRGICOS EN EL TELENCÉFALO DEL RATÓN Papel en el procesamiento de estímulos reforzantes naturales Tesis Doctoral José Martínez Hernández València, 2009 iii D. Fernando Martínez García y D. Enrique Lanuza Navarro, doctores en Biología y Profesores Titulares de los Departamentos de Biología Funcional y Antropología Física y de Parasitología y Biología Celular de la Universidad de Valencia CERTIFICAN Que D. José Martínez Hernandez , licenciado en Biología por la Universitat de València , ha realizado bajo su dirección el trabajo titulado “SISTEMAS DOPAMINÉRGICOS EN EL TELENCÉFALO DEL RATÓN: Papel en el procesamiento de estímulos reforzantes naturales” para la obtención del grado de Doctor en Biología. Para que conste, en cumplimiento de la legislación, firmamos el presente certificado en: Valencia a 29 de mayo de 2009 Dr. Fernando Martínez García Dr. Enrique Lanuza Navarro v Para la realización de esta tesis, el autor ha sido beneficiario de una beca del Programa de Formación de Profesorado Universitario del Ministerio de Educación y Ciencia. Este trabajo se ha enmarcado dentro de los proyectos financiados por el Ministerio de Educación y Ciencia y los fondos FEDER Neurobiología de la atracción sexual: bases neurales del refuerzo inducido por feromonas sexuales (BFU2004-04272/BFI) y Papel de las vias amigdalo-estriatales en el procesamiento del valor reforzante de las feromonas sexuales y sus componentes (BFU2007-67912-C02-01), así como los financiados por la Junta de Comunidades Castilla-La Mancha Vías paralelas de información vomeronasal en la amígdala: una aproximación comportamental (PAC-05-007-2) y La organización de los sistemas quimio- sensoriales y la vía del refuerzo y la adicción (PCC08-0064) vi A mi familia vii “Aún en las ciencias más perfectas nunca deja de encontrarse alguna doctrina exclusivamente mantenida por el principio de autoridad” Santiago Ramón y Cajal “But the reason I call myself by my childhood name is to remind myself that a scientist must also be absolutely like a child. If he sees a thing, he must say that he sees it, whether it was what he thought he was going to see or not. See first, think later, then test. But always see first. Otherwise you will only see what you were expecting. Most scientists forget that. I’ll show you something to demonstrate that later. So, the other reason I call myself Wonko the Sane is so that people will think I am a fool. That allows me to say what I see when I see it. You can't possibly be a scientist if you mind people thinking that you're a fool” Douglas Adams “L’esprit est un produit de l’organisation du cerveau tout comme la vie est un produit de l’organisation des molécules » François Jacob “Mientras el cerebro sea un misterio, el universo continuará siendo un misterio” Santiago Ramón y Cajal “My brain? That´s my second favourite organ.” Woody Allen ix x AGRADECIMIENTOS Ha arribat el moment més personal de tota tesi, en el que has de repassar com es que s’ha aplegat a aquesta situació, i és per això que comence els agraïments en català (encara que després canviaré), perquè així és com la sentisc, encara que estiga en castellà. Han sigut moltes persones les que s’han creuat en el meu camí mentres feia aquesta tesi i d’una manera o altra han tingut un impacte sobre mi i per tant en aquest treball, i per això estic segur que algú m’oblidaré. No m’ho tingueu en compte. Però als primers que de agrair-s’ho són a Fernando i Quique, que em permetreu començar a treballar en el vostre laboratori i amb la vostra tutela i direcció aquesta tesi ha arribat a bon port. De vosaltres dos he aprés principalment el que sé hui en dia de ciència i espere que el futur vos depare encara més èxits. Encara que el laboratori era xicotet, no estava mal acompanyat. Moltes gràcies Amparo, Joana, Carme i Mª José per compartir tantes estones de laboratori i especialment a Amparo que li va tocar ensenyar-me al principi. I en aquest sentit, també li he d’agrair a José, ja que part de esta tesi parteix de la seva. M’agradaria haver passat més temps amb la nova gent que ha entrat. Però el meu temps ja havia passat. I tot això va ocórrer en el immillorable marc de la Facultat de Ciències Biològiques. Moltes gràcies als departaments de Biologia Funcional i Biologia Cellular, que sempre varen facilitar les coses en la mesura del que era possible i per tenir tan bons companys als dos i a la resta de la Universitat. També he d’agrair a Juan Nàcher la oportunitat de treballar al seu laboratori quan es va acabar la meva beca. Em vaig sentir molt agust amb tot l’equip, Carlos, José Miguel i Maria, i especialment a Ramón, Esther, Mª Angeles y Laura que em féreu sentir com un company més. Además, quiero agradecérselo a todos mis amigos, de diferentes ámbitos y diferentes épocas. Muchas gracias a los que estuvieron ahí, pero sobre todo a los que se mantienen. Bea, desde hace ya algunos años has venido ocupando un lugar muy importante entre mis amigos. Echo de menos nuestras carreras por el rio, porque me has ayudado a mantenerme en forma, y más importante, xi por las conversaciones que tuvimos. Espero que todo te vaya siempre muy bien y continuemos coincidiendo en el futuro. Carlos y Dani, compañeros de aventuras durante años, me alegra que continuemos hablando y coincidiendo siempre que es posible, han pasado muchos años desde el instituto y cada vez se hace más complicado, con trabajos diferentes y países diferentes. Pero siempre merece la pena. A tota la colla de “ihuionanem” amb la que he anat a tantes excursions i viatges i hem fet tant quilometres amb les nostres botes mentres discutíem de ciència o de la vida. Espere que puguem fer-ho en el futur de nou. Gràcies a Santi, Raül, Eli, Tonyo, Victor, Salut, Bárbara, Lluís, Ximo, Mª Jesús, Rosa, Gabi, Ángel, Edu, Jorge i tota la resta. Jorge, además de amigo, estuvimos compartiendo piso, al igual que con Carlos, y una lista bastante larga para poner aquí. Muchas gracias a todos por hacer la convivencia tan placentera. A més tinc la sort de comptar amb molts amics de la època de la carrera, alguns dels quals han agarrat el mateix camí de fer una tesi en Neurociències Ximo i Aitana; i alguns en altres camps de la ciència com Mariola, Neus, Anna i Elena; i altres que han agarrat camins completament diferents com Vicent, Reme, Marta, Teto, Varis, Lupe, Dani, Carme, Carles, Ester; Felix i tota la resta que sempre és un plaer retrobar-nos. He de agradecerles también todas las veces que nos hemos juntado en la universidad o fuera de ella, para charlar o cenar. Gracias Santi, Almú, Marta, Sara, Anna y el resto. Gracias también a mis compañeros y compañeras de los cursos de doctorado con los que siempre era bueno juntarse a cenar, Blanca, Aitana, Ana Pérez, Ana Cervera, Cintia, Jordi, Mariana, y a los que no coincidimos en los cursos pero estaban en el laboratorio y de ahí surtió la amistad como Sara y Melissa. Gracias a Bea he conocido mucha gente como sus compis de piso y de laboratorio, y además conocí a Isabel, Jordi, Sonia y Jesús (bueno a Jesús ya le conocía), con los que he pasado buenas cenitas y clases. Moltes gràcies per els vespres de ciència i cervesa, Ignasi, Toni, Miguel, Frago i Use. xii A més vull agrair-li la lluita que fa contra la precarietat en la Ciència a l’organització Joves Investigadors, i més en concret a la gent que vaig conèixer gràcies a l’associació com Isabel, Martina, Dani, Juanvi, Vicent, Pere, Gloria, Jordi, Virgilio, Marta, Santi, Andrés, Paco i tants altres. Además, quiero agradecerles la lucha contra la precariedad a nivel estatal la FJI, Federación de Jóvenes Investigadores, ya que en los últimos años hemos sido testigos de importantes avances, y como no a la gente que conocí en sus listas como Gloria, Tatiana, Lara, Salomón, Nacho, Oscar, Oriol, Natalia, Cecilia, Gloria y muchos más que ahora no puedo recordar. Also, I want to thank to Dr. Satoshi Ikemoto for allowing me to go to his laboratory. And thanks to Rick Shin and his wife and Robert, for being so good lab partners and coffee drinkers. Thanks to Bob, my flat mate and Alex, lab mate, but also travel and adventures partners. Gracias a Isabel Millán por las litografías para la portada. Llegando casi al final, es evidente, que tengo que agradecérselo a mi familia. Tengo que darles las gracias tanto a mis padres y hermano, como a mi abuela, a todos los tíos, tías, primos y primas, somos demasiados, y los que ya nos están. Papá, mamá si Fernando y Quique me educaron en ciencia vosotros, me educasteis en la vida.
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