Understanding ADHD dopaminergic neurotransmission: the p35 KO mice have a preserved D1 but an altered D2 function

FERNANDEZ GUILLERMO; KRAPACHER FAVIO; MARI MACARENA; PAGLINI MARÍA GABRIELA

MAR DEL PLATA

Congreso; XXII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia (SAN); 2017

Attention-deficit hyperactivity disorder (ADHD) is a behavioural condition characterized byatypical levels of inattention, hyperactivity and impulsivity. A recent study suggest a globalprevalence of 3,4 % in children, being the most diagnosed psychiatry disorder at present.Previous studies from our lab have demonstrated that transgenic mice lacking p35 protein(p35KO), the specific activator of Cyclin dependent kinase 5 (Cdk5) exhibit behaviorsresemble those described in animal models of ADHD. P35 KO mice display hyperactivity andless anxiety-like behaviors. Besides, these mice have an increased striatal dopamine (DA)level. These behavioral and biochemical phenotypes are reverted by Methylphenidate and d-Amphetamine, drugs used in ADHD treatment. Since locomotor activity is dependent ondopaminergic neurotransmission, we decided to study the function and expression levels ofthe two main DA receptor, D1 and D2, in the p35 KO mice. We found that striatal D1 and D2contents are similar between p35 KO and Wild Type (WT). To test D1 and D2 function, weused pharmacologic agonist (SKF81297/Quinpirol respectively) and antagonists(SCH23390/Haloperidol respectively) drugs. We found that p35 KO mice have a preserved D1but an altered D2 function, since a low dose of the antagonist Haloperidol (0,03 mg/kg)induces an increase in WT locomotor activity and a decrease in p35 KO. These results mayhelp us to elucidate the mechanism underlying the hyperactivity of this ADHD model..