Pharmacological analysis of Dopamine neurotransmission in hyperactivity mice lacking p35

FAVIO ARIEL KRAPACHER; GUILLERMO FERNÁNDEZ; PAGLINI MARÍA GABRIELA

Huerta Grande, Córdoba

Congreso; XXVII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia (SAN); 2012

SAN

Pharmacological analysis of Dopamine neurotransmission in hyperactivity mice lacking p35. Favio Krapacher, Guillermo Fernandez y Maria Gabriela Paglini. INIMEC-CONICET, Córdoba, Argentina. Background: Previous research in our lab showed that a genetically modified mice lacking p35 (the specific activator of cdk5) exhibit spontaneous hyperactivity, that is ameliorated by the administration of psychostimulants drugs (Krapacher et al. 2010. J Neurochem, 114(1), 203-214). This hyperactivity and its paradoxical response to psychostimulants are related with an impairment in dopaminergic neurotransmission. Objectives: Analyze the functional state of dopaminergic neurotransmission in p35 KO mice through the use of a series of drugs that interfere with the normal function of dopamine receptors. To study the status of the D1 receptor we use the agonist of D1 SKF81297 (5mg/kg ip) and the antagonist SCH23390 (0,05mg/kg ip). In the other hand, to explore the integrity of D2-mediated neurotransmission we administrated the agonist quimpirole (0,5mg/kg ip) and two different doses of the antagonist haloperidol (0,03mg/kg or 0,1mg/kg ip) in wild type (WT) and p35 KO mice. Results: the pharmacological manipulations had the same effect in both animals, producing a reduction of the locomotor activity (by D1r antagonism and D2r agonism/antagonism) or increasing the locomotor activity (D1r agonism). These results indicate that dopamine receptors are totally functional in p35 KO mice, suggesting that the hyperlocomotor behavior of these mice is not direct consequence of dopaminergic receptor alteration.