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

BASMADJIAN OM; ARMONELLI S; OCCHIEPPO VB; MARCHESE NA; BAIARDI G; BREGONZIO C

Berlín

Congreso; 11º FENS Forum of Neuroscience 2018; 2018

Federation of European Neuroscience Societies

Dopamine misbalance, including limbic hyperactivity and cortical hipoactivity, isa hallmark of amphetamine exposure producing endurance sensitization andcognitive alterations. Neuroinflammatory processes are also involved in thesecognitive alterations induced by Amphetamine. Angiotensin II, through AT1receptors (AT1-R) activation, modulates dopamine synthesis and release overlimbic areas, and participates in reward and cognitive responses. Furthermore,its activity has a greater extend as it modulates several stages of the inflammatoryresponse.This work aimed to study AT1-R involvement in sensitization, cognition andneuroinflammatory alterations induced by Amphetamine repeated exposure.Male Wistar rats (250-300g) were used. To study the participation of AT1-R inlong?term Amphetamine effects, the AT1-R blocker Candesartan (CV 3mg/kgp.o.) was administered for 10 days and Amphetamine (2.5 mg/kg i.p.) was dailyadministred from day 6 to 10. On week 3 of Amph withdrawal, working and shortmemory performance was evaluated using Y-maze test and novel objectrecognition respectively. 24h later, the animals were perfused and the brainsprepared for GFAP and CD11b immunohistochemistry to evaluateneuroinflammation. The results were analyzed using 2-way ANOVA followed byBonferroni test.It was found that Amphetamine-sensitization was prevented by AT1-R blockade.Moreover, Amphetamine induce working memory deficit, whereas short memoryremains unaltered. Concomitant with these last results, an increase in astroglialand microglial reactivity was observed only prelimbic prefrotal cortex, structurehighly related with working memory. These structural and functional alterationswere prevented by AT1-R blockade. We conclude that AT1-R activation is a keymediator in the development of Amphetamine-induced sensitization andneuroinflammatory responses, underpinning prelimbic prefrontal functionalalterations.