CONICET | Buscador de Institutos y Recursos Humanos

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 amphetamine produce alterations in brain RAS components that are involved in the expression of the locomotor sensitization to the psychostimulant drug. Wistar male rats, pretreated with amphetamine were used 7 or 21 days later to study AT1 receptors, by immunohistochemistry and western blot, and angiotensinogen mRNA and protein in caudate putamen and nucleus accumbens. In other group of animals treated in the same way, bearing intra-cerebral cannula, the locomotor activity was tested 21 days later, after an amphetamine challenge injection and the animals received an AT1 blocker, losartan or saline 5 min before the amphetamine challenge. An increase of AT1 receptor density induced by amphetamine was found in both studied areas and a decrease in an angiotensinogen mRNA and protein only in CPu at 21 days after treatment, meanwhile no changes were established in NAcc. Finally, the increased locomotor activity induced by amphetamine challenge was blunted by losartan administration in CPu. No differences were detected in the behavioral sensitization when the AT1 blocker was injected in NAcc. Our results support the hypothesis of a key role of brain RAS in the neuroadaptative changes induced by amphetamine.