A New Old Tale: Dopamine Transporter implications in an Attention-Deficit Hyperactivity Disorder (ADHD) animal model.

MARI MACARENA; FERNÁNDEZ GUILLERMO; PAGLINI MARÍA GABRIELA

Córdoba

Congreso; XXXIII Annual Meetin of the Argentine Society of Neuroscience; 2018

SAN

A New Old Tale: Dopamine Transporter implications in an Attention-Deficit Hyperactivity Disorder (ADHD) animal model.Mari Macarena Mariel, Fernández Guillermo, Paglini María Gabriela*Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET-UNC, Córdoba, ARGENTINA:gpaglini@immf.uncor.edu.Attention-Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental condition characterized by atypical levels of inattention, hyperactivity and impulsivity. We have shown that mice lacking the Cdk5 activator, p35 (p35KO), resemble ADHD characteristic phenotypes. P35KO mice show hyperactivity in novel contexts, less anxiety like behaviors and paradoxically response to Amphetamine (AMPH). Furthermore, p35KO display an increased Dopamine (DA) synthesis and a decreased DA metabolism. Given that DA Transporter (DAT) is the target of ADHD treatment drugs and it is functional only when is exposed in surface, the aim of this work was to study total and superficial DAT expression in p35KO and WT Striatal tissue and its modulation by AMPH treatment. Our results show no difference in total DAT levels between WT and p35KO mice. Nevertheless, using synaptosomal surface biotinylation technique, we show significant decreased DAT superficial levels in p35KO mice compared with WT. Besides, AMPH treatment (10 μM for 30 min) of WT synaptosomes induced a decrease in DAT superficial levels, but in p35KO these expression levels remained unaltered. Taken together, our results suggest that the decreased DAT surface expression in p35KO mice correlates with an increased DA availability in synaptic cleft and therefore, an increased locomotor activity. In these sense, our results are critical for the understanding of the mechanism underlying ADHD-like behavioral phenotypes.