The brain RAS is involved in the neuroadaptative responses induced by amphetamine in a two-injection protocol

PAZ MC; MARCHESE, N; STROPPA, M; IMBODEN, H; CANCELA, LM; BREGONZIO, C

Córdoba

Congreso; XXVI Congreso Annual de la Sociedad Argentina de Neurociencia (SAN); 2011

Sociedad Argentina de Neurociencia (SAN)

A single or repeated exposure to psychostimulants induces long-lasting neuroadaptative changes. Different neurotransmitter systems are involved in these responses including the neuropeptide angiotensin II. Our study tested the hypothesis that the neuroadaptative changes induced by AMPH produce alterations in brain RAS components. Wistar male rats (250-300 g), pretreated with AMPH (5mg/kg, ip) were used 7 or 21 days later to quantified AT1 receptors by western blot and mRNA-Angiotensinogen (AOGEN) in caudate putamen (CPu) and accumbens nucleu (NAcc). In another group of animals treated in the same way, bearing intra-cerebral cannula, the locomotor activity was tested after AMPH challenge (0.5 mg/kg) injection. The animals received an AT1 blocker, losartan (8 ug/ul/side) or saline 5 min before the AMPH challenge. We found an increase of AT1 receptors density in both studied areas. AMPH modified the basal and challenge induced expression of mRNA-AOGEN in NAcc and CPu at 7 and 21 days after treatment. Finally The AT1 receptors blockade in NAcc increased the locomotor activity induced by AMPH challenge. Our results support the hypothesis for a key role of brain RAS in the neuroadadptaive changes induced by AMPH.