title: Involvement of the brain renin-angiotensin system (RAS) in the neuroadaptive responses induced by amphetamine in a two-injection protocol.
abstract: 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 also angiotensinogen mRNA and protein in caudate putamen and nucleus accumbens. A second group of animals was used to explore the possible role of Ang II AT1 receptors in the expression of behavioral sensitization. In these 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 5min before the amphetamine challenge. An increase of AT1 receptor density induced by amphetamine was found in both studied areas and a decrease in 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.
authors.affiliation: Instituto de Farmacología Experimental Córdoba (IFEC-CONICET), Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba (UNC), Argentina.
authors.forename: Maria Constanza
authors.initials: MC
authors.lastname: Paz
authors.affiliation: Instituto de Farmacología Experimental Córdoba (IFEC-CONICET), Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba (UNC), Argentina.
authors.forename: Natalia Andrea
authors.initials: NA
authors.lastname: Marchese
authors.affiliation: Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, UNC, Argentina.
authors.forename: Maria Mercedes
authors.initials: MM
authors.lastname: Stroppa
authors.affiliation: Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, UNC, Argentina.
authors.forename: Nelia Marta
authors.initials: NM
authors.lastname: Gerez de Burgos
authors.affiliation: Institute of Cell Biology, University of Bern, Bern, Switzerland.
authors.forename: Hans
authors.initials: H
authors.lastname: Imboden
authors.affiliation: Laboratorio de Neurofarmacología, Instituto de Investigaciones Biológicas y Tecnológicas (IIBYT- CONICET), Universidad Nacional de Córdoba. Facultad de Ciencias Quimicas, Universidad Católica de Córdoba.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Baiardi
authors.affiliation: Instituto de Farmacología Experimental Córdoba (IFEC-CONICET), Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba (UNC), Argentina.
authors.forename: Liliana Marina
authors.initials: LM
authors.lastname: Cancela
authors.affiliation: Instituto de Farmacología Experimental Córdoba (IFEC-CONICET), Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba (UNC), Argentina. Electronic address: bregonzio@fcq.unc.edu.ar.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bregonzio
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000808:Angiotensinogen / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000697:Central Nervous System Stimulants; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D000661:Amphetamine; D019808:Losartan
keywords: AT(1) receptor; Amphetamine; Angiotensin II; Angiotensinogen; Behavioral sensitization