Involvement of the brain renin–angiotensin system (RAS) in the neuroadaptive responses induced by amphetamine in a two-injection protocol

• Published in: Behavioural brain research Vol. 272; pp. 314 - 323
• Main Authors: Paz, Maria Constanza, Marchese, Natalia Andrea, Stroppa, Maria Mercedes, Gerez de Burgos, Nelia Marta, Imboden, Hans, Baiardi, Gustavo, Cancela, Liliana Marina, Bregonzio, Claudia
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 01.10.2014; Elsevier
• Subjects: Amphetamine; Amphetamine - pharmacology; Angiotensin II; Angiotensin II Type 1 Receptor Blockers - pharmacology; Angiotensinogen; Angiotensinogen - metabolism; Animals; AT1 receptor; Behavioral sensitization; Biological and medical sciences; Brain - drug effects; Brain - physiology; Central Nervous System Stimulants - pharmacology; Fundamental and applied biological sciences. Psychology; Losartan - pharmacology; Male; Medical sciences; Motor Activity - drug effects; Motor Activity - physiology; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Random Allocation; Rats, Wistar; Receptor, Angiotensin, Type 1 - metabolism; Renin-Angiotensin System - drug effects; Renin-Angiotensin System - physiology; RNA, Messenger - metabolism; Vertebrates: nervous system and sense organs; Angiotensinogen; Amphetamine; Angiotensin II; Behavioral sensitization; AT1 receptor; CNS stimulant; Psychotropic; Central nervous system; AT1 angiotensin receptor; Prohormone; Encephalon; Renin angiotensin system; AT; receptor; Amfetamine; Sensitization; Behavior; AT receptor
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2014.07.021

•A single dose of amphetamine increases AT1 receptors in CPu and NAcc, 7 and 21 days later.•A single dose of amphetamine decreases angiotensinogen in CPu 21 days later.•Expression of behavioral sensitization to amphetamine is prevented by AT1 receptor blockade. 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.