Involvement of PFC´s Wnt/ β-catenin pathway in cocaine induced sensitization.

SANTIAGO CUESTA; MARÍA J. SEVERIN; JORGELINA BATUECAS; ROSSO SB; ALEJANDRA M. PACCHIONI

Huerta Grande

Congreso; XXVIII Congreso anual de la Sociedad Argentina de Investigaciones en Neurociencia & Reunión satélite/neurobiologia del comportamiento ?Neuroetologia y Neurobiologia de la Memoria en el Cono Sur.; 2013

SAN

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/βcatenin, 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) βcatenin levels in cocaine sensitized animals. Since our main goal was to elucidate the role of Wnt/βcatenin pathway in cocaine sensitization, we evaluate PFC´s GSK3β activity levels of sensitized animals as well as βcatenin 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 GSK3β activity levels associated with a decrease in βcatenin levels in the nucleus, indicating an inhibition of Wnt/βcatenin 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/βcatenin 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/βcatenin pathway