Pretreatment with LiCl blocked development of cocaine induced sensitization by restoring b-catenin levels in specific brain areas

SEVERIN, MA. JULIA; BATUECAS, JORGELINA A.; CUESTA, SANTIAGO; 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 cysteine rich secreted proteins that interact with their receptors: Frizzled, Ryk, and Ror. As a result of their interaction, Dishevelled is activated, and consequently, one of three pathways: Wnt/bcatenin, Planar Cell Polarity, or Wnt/calcium pathways. Wnt signalling pathways are essential for mammalian brain development. However little is known regarding its role in adulthood. Recently, our lab showed that cocaine induce sensitization is associated with a decrease of bcatenin protein levels in Prefrontal Cortex (PFC), Amygdala (Amyg) and Dorsal Striatum (DS). Moreover, bcatenin levels were also decreased in PFC nuclear fraction suggesting that Wnt/bcatenin pathway may be inhibited in cocaine induced sensitization. Therefore our main goal was to elucidate if changes in bcatenin are necessary for locomotor sensitization. Since it is known that Lithium Chloride (LiCl) increases bcatenin levels by inhibition of GSK3b, we administered LiCl or saline i.p. before each cocaine injection. Twenty four hours after testing the behavioral response animals were sacrificed and brain areas were dissected. So far our results showed that systemic LiCl injections blocked cocaine induced sensitization by restoring bcatenin levels in PFC, Amyg and DS, as well as in PFC nuclear fraction. In summary our data showed that changes in bcatenin are essential for cocaine induced sensitization suggesting that Wnt/bcatenin pathway may be involved in cocaine induced neuroadaptations.