BRAIN ANGIOTENSIN II INVOLVEMENT IN THE DEVELOPMENT OF LONG LASTING AMPHETAMINE-INDUCED NEUROINFLAMATION RESPONSES IN PRELIMBIC PREFRONTAL CORTEX RELATED TO WORKING MEMORY DEFICIT

BASMADJIAN, OSVALDO MARTÍN; ARMONELLI, SAMANTA; MARCHESE, NATALIA ANDREA; OCCHIEPPO, VICTORIA BELÉN; BAIARDI, G; BREGONZIO, CLAUDIA

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

10 Sociedades de Biociencias de Argentina

Abstract: Amphetamine (Amph) promotes enduring alteration over neural circuits that can be observed long after. These persistent neuroadaptations also extend to the development of central inflammatory related pathologies, such as glial activation and vascular damage. Angiotensin II, through AT1 receptors (AT1-R) activation, modulates dopamine synthesis and release over limbic areas, and participates in reward and learning responses. Moreover, its activity has a greater extend as it modulates several stages of the inflammatory process in neurons and glia. This work aimed to study AT1-R involvement in neuroinflammatory alterations induced by Amph repeated exposure. Neuroinflammation was evaluated by astrocyte and microglia reactivity at different brain areas, whereas working memory was asses to identify cortical alterations.Male Wistar rats (250-300g) were used. To study the participation of AT1-R in long?term Amph effects, the AT1-R blocker Candesartan (CV 3mg/kg p.o.) was administered for 5 days prior the daily Amph administration (2.5mg/kg i.p x 5 days). On weeks 1 or 3 of Amph withdrawal working memory performance was evaluated using Y-maze test, 24h later the animals were perfused and the brains prepared for GFAP and CD11b immunohistochemistry. The results were analyzed using 2-way ANOVA followed by Bonferroni test. It was found that, at both times analyzed, Amph increased GFAP and CD11B expression only at prelimbic prefrontal cortex concomitant with working memory deficit. These structural and functional alterations were prevented by AT1-R blockade. We conclude that AT1-R activation is a key mediator in the development of Amph-induced neuroinflammatory responses underpinning prelimbic prefrontal functional alterations.