ENHANCED EXPRESSION OF P35 IN SYNAPTOSOMAL FRACCTIONS OF STRIATUM, AFTER ACUTE AND CHRONIC D-AMPHETAMINE ADMINISTRATlON

MLESWKI CECILIA; KRAPACHER FAVIO; PAGLINI GABRIELA

Pinamar, BsAs

Congreso; XX Sociedad Argentina de Neuroquimica (SAN); 2005

XX Sociedad Argentina de Neuroquimica (SAN)

ENHANCED EXPRESS ION OF P35 IN SYNAPTOSOMAL FRACCTIONS OF STRIATUM, AFTER ACUTE AND CHRONIC D-AMPHETAMINEADMINISTRATlON Mleswki C. Krapacher F. Paglini G Ins/. Inv. Médica M. y M. Ferreyra-INIMEC-CONICE´J: Córdoba. Argen/illa. E-mail: cmleswki@immfllllcor.edu The cellular and molecular mechanisms of sensitization in addictive process are still unclear. Chronic cocaine administration up-reguJates the expression of cyclin-dependent kinase 5 (Cdk5) and its activator p35 in striatum through the induction of Delta FosB. It would be reasonable to consider that cdk5/p35 modulates the etTects of psichostimulants administration; in which the increase ofcdk5/p35 expression and activity would be dircctcd to specific targets that regulate signaling pathway proteins which counterbalances the sensitized behaviors. Our goal is to obtain new and detailed behavioral and biochemical evidences about the participation of cdk5/ p35 in D-amphetarnine sensitization process. We have found that acute and chronic D-Amphetarnine treatment, in periadolescent rats, can induce cdk5 activity in striatum as weIl as the increase and translocation of its actívator, p35, from cytosolic to membrane synaptosomal fraction. In addition. chronic D-Amphetarnine trcated p35 KO mice showed significantly reduced locomotor activity comparcd with WT micc. The presents results indicate that cdk5/ p35 signaling could participate in the in the acute and chronic D­-Amphetamine-induced behavioral and ceIlular evcnts during the development and expression of sensitizatíon. The knowledge of cellular and molecular mechanisms in drugs abuse addiction would profit the development ofmore efficient therapies in drug addiction pathologies.