Lack of Cdk5 activity is involved on Dopamine Transporter expression and function: Evidences from an animal model of Attention-Deficit Hyperactivity Disorder

FERNÁNDEZ, GUILLERMO; KRAPACHER, FAVIO; FERRERAS, SOLEDAD; QUASSOLLO, GONZALO; MARI, MACARENA MARIEL; PISANO, MARÍA VICTORIA; MONTEMERLO, ANTONELLA; RUBIANES, MARÍA DOLORES; BREGONZIO, CLAUDIA; ARIAS, CARLOS; PAGLINI, MARÍA GABRIELA

EXPERIMENTAL NEUROLOGY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2021 vol. 346

0014-4886

ttention deficit/Hyperactivity disorder (ADHD) is one of the most diagnosed psychiatric disorders nowadays.The core symptoms of the condition include hyperactivity, impulsiveness and inattention. The main pharmacologicaltreatment consists of psychostimulant drugs affecting Dopamine Transporter (DAT) function. We havepreviously shown that genetically modified mice lacking p35 protein (p35KO), which have reduced Cdk5 activity,present key hallmarks resembling those described in animal models useful for studying ADHD. The p35KOmouse displays spontaneous hyperactivity and shows a calming effect of methylphenidate or amphetaminetreatment. Interestingly, dopaminergic neurotransmission is altered in these mice as they have an increasedDopamine (DA) content together with a low DA turnover. This led us to hypothesize that the lack of Cdk5 activityaffects DAT expression and/or function in this animal model. In this study, we performed biochemical assays,cell-based approaches, quantitative fluore