Amphetamine neuroadaptations involve neurocognitive alterations: angiotensin II AT1 receptors role

MARCHESE NA; OCCHIEPPO V; BASMADJIAN OM; BAIARDI G

Córdoba

Congreso; III Reunión Internacional de Ciencias Farmacéuticas; 2014

UNC-UNR-CONICET

The Renin-Angiotensin System (RAS) was firstdescribed as a peripheral hormonal system. Over the years several local RAShave been described in different organs. In the brain, the RAS is awelldocumented neuromodulator of multiple brain circuits. AT1 receptor (AT1-R)activation is involved in learning and memory processes, in the stress responseand in catecholamine neurotransmission. Exposure to amphetamine (AMPH) inducesneuroadaptations that modify behavioral responses to future pharmacological orenvironmental challenges. Alterations in working, recognition and long term memoryhave been reported in AMPH users. Our aim was to evaluate the involvement ofbrain RAS, through its AT1-R, on long term amphetamineinduced modifications inlearning processes. Wistar male rats (250-300g) treated with AT1-R blocker(candesartan 3 mg/kg p.o., days 1-5), followed by AMPH (2,5 mg/kg, ip, days6-10), were evaluated 1 week later on the passive avoidance test afterreceiving a pharmacological (AMPH 0.5 mg/kg) or physiological (cold stress: 4ºCfor 4 h) challenge. Following the test session, the animals were sacrificed andthe brains were processed for c-fos immunoreactivity (fos-IR) as a marker ofneuronal activation. The results were analyzed with Kruskal Wallis test (steptrough latencies) and ANOVA (fos- IR). The results indicated that history ofrepeated AMPH administration does not allow the expression of the deleteriouseffect in long term memory induced by acute exposure to AMPH or cold stress. Inboth situations the AT1-R blockade prevented this modified response. C-fosexpression in the hippocampus, indicates a diminished neuronal activation inanimals receiving an AMPH or cold stress challenge in all studied groups. Inagreement with our previous findings, we conclude that AT1-R play an activerole in AMPH-induced neuroadaptations altering learning and memory processes.It should be taken in consideration the potential use of AT1 receptorantagonist in the therapy of drug of abuse disorders.