Modulation of glucocorticoid receptor activity by CB1 cannabinoid receptor signaling. Its role on memory consolidation of emotionally aroused experiences.

GRANJA-GALEANO G; ZAPIA D; ZORRILLA ZUBILETE, M.A.; FRANCHI AM.; MONCZOR F.; DOMÍNGUEZ RUBIO AP; FITZSIMONS CP

Mar del Plata

Congreso; LXI Reunión Científica de la Sociedad Argentina de Investigación Clínica (SAIC); 2016

SAIC-SAFE

The cannabinoidreceptor type 1 (CB1) and the glucocorticoid receptor (GR) are coexpressed inseveral brain areas involved in learning and memory, including hippocampus. Ithas been suggested that the CB1 signaling modulates GR-mediated processesregulating its activity. Glucocorticoids mediate the behavioral consequences ofstress, such as the memory consolidation associated with emotional events. Thedownstream immediate-early gene Egr1 is a molecular target of GR, known to beinvolved in regulating this process. In this work we studied the role of theCB1 on GR-mediated gene expression involved in the consolidation of arousalinfluenced memory. For in-vitro studies, we worked with HT22 cell line, derivedfrom murine hippocampus. In these cells, Dexamethasone (Dex) induction of Egr1was potentiated (300%, p<0.05) by the selective CB1 agonist meta-anandamide.To study if this modulation is also present in-vivo, we studied the expressionof Egr1 in the hippocampus of male CD1 mice carrying a knock out mutation forthe CB1 receptor gene (KO) and their naive counter-part (WT). In WT strain, 6hours treatment with Dex (1,5 mg/kg; i.p.) produced a two-fold increase inEgr1. The co-treatment with the CB1 agonist HU210 (0,1 g/kg, i.p.) was able toinduce a threefold increment, whereas the CB1 antagonist AM251 (1 g/kg)completely blocked the Dex-induced Egr1 expression.Consistently, in KO mice Dex did not induced Egr1 expression, and no effect wasobserved by cotreatment with HU210 or AM251. When associative memory wasevaluated with a passive-avoidance task, Dex treatment in WT mice immediatelyafter a 0,2 mA for 2s of shock, facilitated memory consolidation. On the otherhand, KO mice were incapable to consolidate associative memory neither underbasal conditions or Dex treatment. Our results suggest that the endocannabinoidsystem plays a necessary role in memory consolidation , modulatingglucocorticoid signaling.