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

BASMADJIAN, O.M.; ARMONELLI, S; OCCHIEPPO. V.B.; MARCHESE, N.A.; BAIARDI, G.; BREGONZIO, C.

Congreso; 11th FENS FORUM; 2018

Federation of European Neuroscience Societies

Dopamine misbalance, including limbic hyperactivity and cortical hipoactivity, is a hallmark of amphetamine exposure producing endurance sensitization and cognitive alterations. Neuroinflammatory processes are also involved in these cognitive alterations induced by Amphetamine. Angiotensin II, through AT1 receptors (AT1-R) activation, modulates dopamine synthesis and release over limbic areas, and participates in reward and cognitive responses. Furthermore, its activity has a greater extend as it modulates several stages of the inflammatory response.This work aimed to study AT1-R involvement in sensitization, cognition and neuroinflammatory alterations induced by Amphetamine repeated exposure.Male Wistar rats (250-300g) were used. To study the participation of AT1-R in long?term Amphetamine effects, the AT1-R blocker Candesartan (CV 3mg/kg p.o.) was administered for 10 days and Amphetamine (2.5 mg/kg i.p.) was daily administred from day 6 to 10. On week 3 of Amph withdrawal, working and short memory performance was evaluated using Y-maze test and novel object recognition respectively. 24h later, the animals were perfused and the brains prepared for GFAP and CD11b immunohistochemistry to evaluate neuroinflammation. The results were analyzed using 2-way ANOVA followed by Bonferroni test.It was found that Amphetamine-sensitization was prevented by AT1-R blockade. Moreover, Amphetamine induce working memory deficit, whereas short memory remains unaltered. Concomitant with these last results, an increase in astroglial and microglial reactivity was observed only prelimbic prefrotal cortex, structure highly related with working memory. 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 Amphetamine-induced sensitization and neuroinflammatory responses, underpinning prelimbic prefrontal functional alterations.