Rafael Maldonado

Group website

Research Outline

Our main interest is the identification of new therapeutical targets at the nervous system level.  The group has focused its activities in the neurochemical and neuroanatomical bases of the dependence to opioids and cannabinoids employing murine models. We have also studied the possible use of some of these compounds in the treatment of pain, cognitive, affective and eating disorders. Therefore, we use a classical pharmacological strategy complemented with the use of genetically modified animals, in particular, knockout mice, and biochemichal techniques to quantify in vivo the concentration of several monoamines. We are also interested in studying the involvement of the endogenous opioid (EOS), cannabinoid (ECS) and hipocretinergic (EHS) systems in the physiopathology of affective disorders and cognitive deficits.

 

Research Lines

  • Involvement of the EOS in addiction (nicotine, cocaine)

  • New therapeutic approaches for drug addiction treatment.

  • EOS and ECS involvement in palatable food-seeking behaviour. 

  • EOS, ECS and serotonergic system role in neuropathic, osteoarthritic and inflammatory pain, search for new pharmacological targets and analgesic compounds.

  • ECS participation in alcohol consumption vulnerability. 

  • Evaluation of acylethanolamide-based neuroprotectants in brain hypoxia preclinical models. 

  • EHS involvement in addiction (nicotine, cannabinoids) and in the mechanisms underlying aversive memories (consolidation and extinction). 

  • Cognitive deficits associated with nicotine withdrawal.

  • Molecular and cellular mechanisms (mTOR) involved in the ECS-controlled cognitive function.

  • Targeting the ECS for pharmacological therapies in FXS.

  • Brain effects of chronic THC exposure (cognitive and motor coordination deficits).

  • Eating disorders and chronic pain mechanisms using RiboTag technology.

  • Loss of control of palatable food-seeking behavior using DREADD approach.

  • Nursing procedures-associated pain and non-communicative pain bioethics in critical care patients.

  • Clinical differences in patients afflicted by vulvodinia using psychometric tools.

 

Team during 2017-18

  • Other PIs: Josep-Eladi Baños Díez, Fernando Berrendero Díaz, Andrés Ozaita Mintegui, Elena Martín García, Miquel A. Martín Sánchez.
  • Postdocs: David Cabañero Ferri, Antonio Ortega Álvaro, Roberto Cabrera Ortega, Virginia Mela Rivas, Aurelijus Burokas, Maria Sanchis Ollé and Juan Antonio Ortega Sánchez.
  • PhD students: Roger Negrete Buela, Maria Gomis González, Itzel Montserrat Lara Mayorga, Elk Kossatz de Mello, Míriam Gutiérrez Martos, Victoria Salgado Mendialdúa, Rocío Saravia Santos, Sami Kummer, Alba Navarro Romero, Miriam Martínez Navarro, Mireia Carcolé Estrada, Laura Domingo Rodríguez, Sara Martínez Torres, Ángela Ramírez López, Alejandra Escudero Lara, Lorena Galera López, Sheila Piedra Barrull Ana M. Gallego Román, Anna Vázquez Oliver, Eric Senabre Marchán, Pablo Calvé Pérez, Cecilia Teresa Brambilla Pisoni and Pilar Ortiz Teba.
  • Technicians: Raquel Martín García, Dulce Real Muñoz, Francisco Porrón López, Marta Linares López, Mireia Viñas Noguera, Eva María Andrés Serna, Jessica Tijero Santos and Neus Morgui Valls.
  • Project manager: Miquel-Àngel Serra Beltrán.
  • Research visits:
    • Graciela N. Balerio (PI, Academic collaborator, University of Buenos Aires-CONYCET, Argentina, Feb-Mar 2017, Jul-Aug 2017 and Jul 2018).
    • Oliver Garnham (ERASMUS undergraduate student, University of Surrey, UK, Sep 2016-Jun 2017).
    • Emily Flores (UPF summer program undergraduate student, University of Richmond VA, USA, Summer 2017).
    • Matt Reilly (UPF summer program undergraduate student, University of Richmond VA, USA, Summer 2017).
    • Tom Cox (ERASMUS undergraduate student, University of Surrey, UK, Sep 2017-Jun 2018).
    • Rachel Leah Frimerman (Pre-Med student, Touro College New York NY, USA, Sep 2017-Feb 2018).
    • Benjamin W. Fait (FULBRIGHT fellow, Yale University CT, USA, Sep 2017-Jun 2018).
    • Federica Servillo (ERASMUS undergraduate student, University of Perugia, Italy, May-Sep 2018).
    • Marnie Barham (ERASMUS undergraduate student, Surrey Univ, UK, Sep 2018-Jun 2019).

 

Selected publications

  • Charbogne P, Gardon O, Martín-García E, Keyworth HL, Matsui A, Mechling AE, Bienert T, Nasseef T, Robé A, Moquin L, Darcq E, Ben Hamida S, Robledo P, Matifas A, Befort K, Gavériaux-Ruff C, Harsan LA, von Elverfeldt D, Hennig J, Gratton A, Kitchen I, Bailey A, Alvarez VA, Maldonado R, Kieffer BL (2017) Mu opioid receptors in gamma-aminobutyric acidergic forebrain neurons moderate motivation for heroin and palatable food. Biol Psych, 81(9):778-788. doi: 10.1016/j.biopsych.2016.
  • Saravia R, Flores A, Plaza-Zabala A, Busquets-García A, Pastor A, de la Torre R, Di Marzo V, Marsicano G, Ozaita A, Maldonado R, Berrendero F (2017). CB1 cannabinoid receptors mediate cognitive deficits and structural plasticity changes during nicotine withdrawal. Biol Psych, 81(7):625-634. doi: 10.1016/j.biopsych.2016. 07.007.
  • Maldonado R, Baños JE, Cabañero D (2018) Usefulness of knockout mice to clarify the role of the opioid system in chronic pain. Br J Pharmacol, 175(14):2791-2808. doi: 10.1111/bph.14088.
  • Burokas A*, Martín-García E*, Espinosa-Carrasco J*, Erb I, McDonald J, Notredame C, Dierssen M, Maldonado R (2018) Extinction and reinstatement of an operant responding maintained by food in different models of obesity. Addict Biol, 23(2):544-555. doi: 10.1111/adb.12597.
  • Ben Hamida S, Mendonça-Netto S, Arefin TM, Nasseef MdT, Boulos L-J, McNicholas M, Ehrlich AT, Clarke E, Moquin L, Gratton A, Darcq E, Harsan LA, Maldonado R, Kieffer BL (2018) Increased alcohol seeking in mice lacking GPR88 involves dysfunctional mesocorticolimbic networks.Biol Pysch, 84(3):202–212. doi: 10.1016/j.biopsych.2018. 01.026.

 

Other relevant information 2017-18

Patents 

Title: Use of cannabidivarin in the treatment of autism spectrum disorder, associated disorders and schizophrenia

Inventors: Geoffrey Guy, Stephen Wright, James Brodie, Marie Wooley-Roberts, Rafael Maldonado, Daniela Parolaro, Livio Luongo, Joanne Neill.

Application number: PCT/GB2017/051007

Application date: 11/4/2017

Priority date: 11/4/2017

Publication Number: WO2017178807 A1

Publication date: 19/10/2017

Holding entity: GW Pharma Limited

 

Title: Use of cannabidiolic acid in the treatment of autism spectrum disorder and associated disorders

Inventors: Geoffrey Guy, Stephen Wright, James Brodie, Marie Wooley-Roberts, Rafael Maldonado, Daniela Parolaro, Livio Luongo, Joanne Neill.

Application number: PCT/GB2017/051010

Application date: 11/4/2017

Priority date: 11/4/2017

Publication date: 19/10/2017

Publication number: WO2017178810 A1

Holding entity: GW Pharma Limited

 

Organisation of conferences, workshops and Summer Schools

Maria Gomis González, Míriam Gutiérrez Martos, Victoria Salgado Mendialdúa, Rocío Saravia Santos, Alba Navarro Romero, Miriam Martínez Navarro, Mireia Carcolé Estrada, Laura Domingo Rodríguez, Sara Martínez Torres, Ángela Ramírez López, Alejandra Escudero Lara, Lorena Galera López, Sheila Piedra Barrull Ana M. Gallego Román, Anna Vázquez Oliver, Mireia Viñas, Miquel-Àngel Serra and Andrés Ozaita Mintegui, Workshop on the effect of drugs in the brain and on the neurobiological substrate of several neuropsychiatric disorders, addressed to Primary and Second ary School students, Youth Mobile Festival (YOMO) of the Mobile World Congress (MWC), Barcelona, Spain (Feb 2017)

 

Invitations as keynote speaker

Rafael Maldonado, Keynote lecture: “The endocannabinoid system and neuropathic pain”, 10th Congress of the European Pain Federation (EFIC), Copenhagen, Denmark (Sep 2017).

Rafael Maldonado, Keynote lecture “Involvement of the endocannabinoid system in addictive behaviour”, Biennal Meeting of the Addictive Chapter of the Italian Society of Pharmacology, Varese, Italy (May 2018).