AMPHETAMINE NEUROADAPTATIONS INVOLVE NEUROCOGNITIVE ALTERATIONS: ANGIOTENSIN II AT1 RECEPTORS ROLE.

MARCHESE NA; OCCHIEPO V; BASMADJIAN M; BAIARDI, G; BREGONZIO C

CORDOBA

Congreso; III Reunión Internacional de Ciencias Farmacéuticas; 2014

UNC-UNR-CONICET

The Renin-Angiotensin System (RAS) was first described as a peripheralhormonal system. Over the years several local RAS have been described in differentorgans. In the brain, the RAS is a well-documented neuromodulator of multiple braincircuits. AT1 receptor (AT1-R) activation is involved in learning and memory processes,in the stress response and in catecholamine neurotransmission.Exposure to amphetamine (AMPH) induces neuroadaptations that modifybehavioral responses to future pharmacological or environmental challenges.Alterations in working, recognition and long term memory have been reported inAMPH users.Our aim was to evaluate the involvement of brain RAS, through its AT1-R, onlong term amphetamine-induced modifications in learning processes.Wistar male rats (250-300g) treated with AT1-R blocker (candesartan 3 mg/kgp.o., days 1-5), followed by AMPH (2,5 mg/kg, ip, days 6-10), were evaluated 1 weeklater on the passive avoidance test after receiving a pharmacological (AMPH 0.5 mg/kg)or physiological (cold stress: 4ºC for 4 h) challenge. Following the test session, theanimals were sacrificed and the brains were processed for c-fos immunoreactivity (fos-IR) as a marker of neuronal activation. The results were analyzed with Kruskal Wallistest (step trough latencies) and ANOVA (fos- IR).The results indicated that history of repeated AMPH administration does notallow the expression of the deleterious effect in long term memory induced by acuteexposure to AMPH or cold stress. In both situations the AT1-R blockade prevented thismodified response. C-fos expression in the hippocampus, indicates a diminishedneuronal activation in animals receiving an AMPH or cold stress challenge in all studiedgroups.In agreement with our previous findings, we conclude that AT1-R play an activerole in AMPH-induced neuroadaptations altering learning and memory processes. Itshould be taken in consideration the potential use of AT1 receptor antagonist in thetherapy of drug of abuse disorders.