Involvement of PFC´s Wnt/b-catenin signaling pathway in cocaine induced-sensitization

CUESTA, SANTIAGO; SEVERIN, MA. JULIA; BATUECAS, JORGELINA A.; ROSSO, SILVANA B; PACCHIONI AM

Huerta Grande-Cordoba

Congreso; XXVIII Congreso Anual de la Sociedad Argentina de Investigaciones en Neurociencias; 2013

Sociedad Argentina de Investigaciones en Neurociencias

Wnt factors are cistein rich secreted proteins that interact with their receptors: Frizzled, Ryk, and Ror. As a result of the interaction, Dishevelled is activated, and,consequently, one of three pathways: Wnt/bcatenin, Planar Cell Polarity, or Wnt/calcium pathways. Wnt signaling pathways are essential for mammalian brain development. However, little is known regarding its role in adulthood. Recently we showed a decrease in Prefrontal Cortex (PFC) bcatenin levels in cocaine sensitized animals. Since our main goal was to elucidate the role of Wnt/bcatenin pathway in cocaine sensitization, we evaluate PFC´s GSK3b activity levels of sensitized animals as well as bcatenin levels in nuclear fraction. Adult male Wistar rats received daily cocaine injections for 7 days, were tested for locomotor sensitization and sacrificed 24hs after last injection. Our results showed an increase in GSK3b activity levels associated with a decrease in bcatenin levels in the nucleus, indicating an inhibition of Wnt/bcatenin pathway in PFC. Then, we evaluate if these PFC changes were necessary for cocaine sensitization. To do it, rats received an intra-PFC infusion of Sulindac an hour before cocaine between day 2 and 6 of the treatment. The data showed that blocking PFC Wnt/bcatenin pathway with Sulindac, prior to cocaine injections, enhances the development of behavioral sensitization. So far our data suggests that cocaine sensitization is associated with an inhibition of PFC Wnt/bcatenin pathway.