Cocaine induced sensitization is associated with decrease activity of the Wnt/βcatenin pathway in Dorsal Striatum

S. CUESTA; FUNES A; ROSSO SB; A.M.PACCHIONI

Huerta Grande

Congreso; XIX Congreso Anual de la Sociedad Argentina de Investigaciones en Neurociencia; 2014

Sociedad Argentina de Investigación en Neurociencia.

In the case of the Wnt canonical or Wnt/β catenin pathway, the interaction between Wnt and Frizzled results in the activation of Dishevelled; which in turn, inhibits GSK-3β and stabilize β catenin. We recently found that Wnt canonical pathway is differentially involved in cocaine induced sensitization. For instance, its inhibition in Prefrontal Cortex is essential for development of cocaine sensitization; while an increased activity in Nucleus Accumbens is necessary for the expression. Since our main goal is to elucidate the role of Wnt/β catenin pathway in cocaine sensitization, we also investigated whether or not changes in the Dorsal Striatum (DS) have a significant role in it. In order to do that, adult Wistar rats received daily cocaine injections for 7 days. All animals were tested for cocaine induced locomotor activity on days 1 and 7, while one group was also tested on day 28. They were sacrificed 24hs after day 7 or 28. Our results showed that cocaine induced a decrease in Wnt/β catenin pathway signaling in DS in order to exhibit behavioral sensitization either after day 7 or 28. Even though a pharmacological inhibition of this pathway in DS did not induce behavioral sensitization. On the other hand, after 21 days of abstinence the pathway activity is increased in DS. So far our data suggests that changes in the Wnt/ β catenin pathway in DS are necessary but not sufficient to induce behavioral sensitization.