PSICOESTIMULANTES Y CEREBRO

In our lab we are studying some cellular and molecular mechanisms involved in the process of addiction to drugs of abuse, specifically amphetamines and their derivatives such as methylphenidate. We are particularly interested in understanding the neuroadaptive responses provoked by stimulant drugs that involve functional and structural synaptic plasticity. We focus our attention on the articipation of "Cdk5/p35" kinase complex as a neuroadaptive-key modulator..

Furthermore, and considering that psychostimulants are the medication of choice for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children and adolescent, we investigate the neurobiology of ADHD using an transgenic animal model lacking “p35” protein of Cdk5/p5 complex. This mouse mimics the core features of ADHD, includes hyperactivity, impaired action inhibition and paradoxical response to psychostimulants, particularly methylphenidate (Ritalin). Currently, ADHD is one of the most diagnosed psychiatric disorders in children, with a worldwide prevalence of 4%. So far, there is no biological marker for its diagnosis. Therefore, the development of animal models is a powerful tool to elucidate genetic and neurological underpinnings of ADHD-related disorders and as a platform for medication development.

 

LABORATORY MEMBERS:

 

Est. Macarena Mari

Student of Biological Science-UNC.

Tesinist

macarena_mari@hotmail.com

 

Med. Sebastián Leonangeli

PhD student

sleonangeli@hotmail.com

 

PAST LABORATORY MEMBERS:

Dra. Mariana Paolorrosi

Dra. Cecilia Mlewski

Dr. Carlos Arias

Dr. Favio Krapacher

Dra. Soledad Ferreras

Dra. M. Victoria Pisano

Dr. Damian Revillo

Dra. Evelin Cotella

Biol. Antonella Scarponi Gómez

Dr. Guillermo Fernández

 

Grants:

CONICET- FONCyT – SeCyT-UNC

PUBLICATION (LAST 10 YEARS)

  1. Long-term impact of chronic variable stress in adolescence versus adulthood. 2018. Cotella EM, Gomez AS, Lemen P, Chen C, Fernández G, Hansen C, Herman JP, Paglini MG. Prog Neuropsychopharmacol Biol Psychiatry. Aug 7. pii: S0278-5846(18)30313-0. doi: 10.1016/j.pnpbp.2018.08.003. [Epub ahead of print].
  2.  Cdk5 Is Essential for Amphetamine to Increase Dendritic Spine Density in Hippocampal Pyramidal Neurons. 2017. Ferreras S, Fernández G, Danelon V, Pisano MV, Masseroni L, Chapleau CA, Krapacher FA, Mlewski EC, Mascó DH, Arias C, Pozzo-Miller L, Paglini MG. Front Cell Neurosci. Nov 24;11:372. doi: 10.3389/fncel.2017.00372.
  3. Association between the expression of amphetamine-induced behavioral sensitization and Cdk5/p35 activity in Dorsal Striatum. 2016. Mlewski, M., Arias, C. and Paglini, G. Behavioral Neuroscience. 2016;130(1):114-22.
  4.  Reinstatement of an extinguished fear conditioned response in infant rats. 2015. Revillo, D. A., Trebucq, G., Paglini, G. & Arias, C. Learning & Memory. 2015 Dec 15;23(1):1-8.
  5.  Contextual learning and context effects during infancy: 30 years of controversial research revisited. 2015. Revillo Damián, Cotella Evelin M, Paglini Gabriela, Arias Carlos. Physiology and Behavior. 2015  ep 1;148:6-21. Review.
  6. Spontaneous recovery from extinction in the infant rat. 2014. Revillo DA, Paglini MG, Arias C. Behav Brain Res. 12;274:149-157. doi: 10.1016/j.bbr.2014.08.009.
  7. A sensory-enhanced context allows renewal of an extinguished fear response in the infant rat. 2013. Revillo DA, Molina JC, Paglini MG, Arias C. Behav Brain Res, Sep 15;253:173-7
  8.  Reacquisition, reinstatement and renewal of a conditioned taste aversion in preweanling rats. 2013. Revillo, D. A. a, Castello, S. a, Paglini, G. a and Arias, C. Dev Psychobiol, May;56(4):713-25. Epub 2013 Jun 13.
  9. Re-examining the ontogeny of the context preexposure facilitation effect in the rat through multiple dependent variables. 2012. Pisano MV; Ferreras S; Krapacher FA; Paglini G*; Arias C*. Behav Brain Res., Jul 15;233(1):176-90. *These authors shared the last authorship.
  10. Odor-avoidance or odor-preference induced by amphetamine in the infant rat depending on the dose and testing modality. 2012. Revillo DA, Fernández G, Castello S, Paglini MG, Arias C. Behav Brain Res., May 16;231(1):201-7.
  11. Mice lacking p35 display hyperactivity and paradoxical response to psychostimulants. 2010. FA Krapacher, EC Mlewski, S Ferreras, M Paolorossi, V Pisano, C Hansen and G Paglini. J Neurochem., 114: 203-214.
  12. Previous stress exposure enhances both anxiety-like behaviour and p35 levels in the basolateral amygdala complex: modulation by Midazolam. 2010. Bignante, EA, Paglini, G and Molina VA. Eur Neuropsychopharmacol. Jun; 20(6):388-397.
  13. Dopamine receptors modulate ethanol's locomotor-activating effects in preweanling rats.  010. Arias C, Mlewski EC, Hansen C, Molina JC, Paglini MG, Spear NE. Dev Psychobiol Jan;52(1):13-23.
  14. Transient enhanced expression of cdk5 activator p25 after acute and chronic d-amphetamine administration. 2008. Mlewski Estela Cecilia, Krapacher Favio Ariel, Ferreras Soledad and Paglini Gabriela. Ann N Y Acad Sci., 1139: 89-102.