Association Between the Expression of Amphetamine-Induced Behavioral Sensitization and Cdk5/p35 Activity in Dorsal Striatum

MLEWSKI ESTELA CECILIA; ARIAS CARLOS; PAGLINI GABRIELA

BEHAVIORAL NEUROSCIENCE.

AMER PSYCHOLOGICAL ASSOC

Lugar: Washington DC, (USA); Año: 2016 vol. 130 p. 114 - 122

0735-7044

Sensitization to psychostimulants is strongly influenced by the environmental context in which the drugis administered and little is known about the molecular mechanisms that regulate this process. Chronictreatment with psychostimulants has been shown to upregulate the expression of cyclin-dependent kinase5 (Cdk5) in the striatum, as a downstream target gene of FosB. This study was therefore designed toanalyze neurochemical changes underlying the expression of amphetamine-induced sensitization. To thisend, periadolescent rats were given saline or 4 mg/kg amphetamine in a NOVEL or a HOME environment.After 1 day, subjects were challenged with vehicle or 2 mg/kg amphetamine in the same contextin which they received the first administration of the drug. Locomotor activity and the expression levelsof p35 and Cdk5 activity in synaptosomes of the dorsal striatum were analyzed. The expression ofbehavioral sensitization was observed only in the NOVEL condition. Furthermore, only animals trainedand tested in the NOVEL condition showed increased p35 protein levels and Cdk5 activity. Our findingsprovide clear behavioral and neurochemical evidence of a specific association between increased p35 andCdk5 activity in the dorsal striatum and the expression of amphetamine-behavioral sensitization, allowingus to propose p35 as a biochemical marker of behavioral sensitization to amphetamine.