Brain and Psychostimulants
Our lab studies some of the molecular and cellular mechanisms implicated in the process of addiction to drugs of abuse. In particular, we study amphetamines and its derivates.
We are interested in understanding the neuroadaptive responses evoked by stimulant drugs involving functional and structural synaptic plasticity. We are particularly focused in the actions of the “Cdk5/p35” protein complex as a key modulator of these neuroadaptive responses.
Considering that physchostimulant drugs are the main pharmacological treatment for ADHD in children and adolescents, we study the neurobiological basis of this disorder using a transgenic mouse model. This mouse is deficient for the “p35” protein from the Cdk5/p35 complex and it presents some features that are associated with the disorder in humans. Currently, ADHD is one of the most broadly diagnosed disorder in kids and adolescents, with a worldwide prevalence of 3.4%. Usual treatment, paradoxically, involves psychostimulants, in particular methylphenidate (Ritalin). Nowadays, there are no biological markers with diagnostic value for this condition.
Therefore, the availability of animal models are invaluable tools to unscramble the molecular and cellular mechanisms underlying the neurophysiological characteristics of the disorder, and provide a great opportunity to screen potential therapeutic strategies.
- CONICET- FONCyT – SeCyT-UNC
CURRENT LAB MEMBERS:
Med. Sebastián Leonangeli
Est. Macarena Mari
Studente Ciencias Biológicas, UNC.
FORMER LAB MEMBERS:
Dra. Mariana Paolorrosi
Dra. Cecilia Mlewski
Dr. Favio Krapacher
Dra. Soledad Ferreras
Dra. M. Victoria Pisano
Dr. Carlos Arias
Dr. Damián Revillo
Dra. Evelin Cotella
Biol. Antonella Scarponi Gómez
Dr. Guillermo Fernández
LAST 10 YEARS MOST RELEVANT PUBLICATIONS
- 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. 2019; 88: 303-10 doi: 10.1016/j.pnpbp.2018.08.003.
- 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.
- 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.
- 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.
- 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 Sep 1;148:6-21. Review.
- 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. .
- A sensory-enhanced context allows renewal of an extinguished fear response in the infant rat. Revillo DA, Molina JC, Paglini MG, Arias C. Behav Brain Res, Sep 15;253:173-7.
- 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.
- 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.
- 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.
- 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.
- 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.
- Dopamine receptors modulate ethanol's locomotor-activating effects in preweanling rats. 2010. Arias C, Mlewski EC, Hansen C, Molina JC, Paglini MG, Spear NE. Dev Psychobiol Jan;52(1):13-23.
- 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.