title: Brain Angiotensin II AT1 receptors are involved in the acute and long-term amphetamine-induced neurocognitive alterations.
abstract: BACKGROUND
  Angiotensin II, by activation of its brain AT1-receptors, plays an active role as neuromodulator in dopaminergic transmission. These receptors participate in the development of amphetamine-induced behavioral and dopamine release sensitization. Dopamine is involved in cognitive processes and provides connectivity between brain areas related to these processes. Amphetamine by its mimetic activity over dopamine neurotransmission elicits differential responses after acute administration or after re-exposure following long-term withdrawal periods in different cognitive processes.
  
  
  OBJECTIVE
  The purpose of this study is to evaluate the AT1-receptor involvement in the acute and long-term amphetamine-induced alterations in long-term memory and in cellular-related events.
  
  
  METHODS
  Male Wistar rats (250-300 g) were used in this study. Acute effects: Amphetamine (0.5/2.5 mg/kg i.p.) was administered after post-training in the inhibitory avoidance (IA) response. The AT1-receptor blocker Losartan was administered i.c.v. before a single dose of amphetamine (0.5 mg/kg i.p.). Long-term effects: The AT1-receptors blocker Candesartan (3 mg/kg p.o.) was administered for 5 days followed by 5 consecutive days of amphetamine (2.5 mg/kg/day, i.p.). The neuroadaptive changes were evidenced after 1 week of withdrawal by an amphetamine challenge (0.5 mg/kg i.p.). The IA response, the neuronal activation pattern, and the hippocampal synaptic transmission were evaluated.
  
  
  RESULTS
  The impairing effect in the IA response of post-training acute amphetamine was partially prevented by Losartan. The long-term changes induced by repeated amphetamine (resistance to acute amphetamine interference in the IA response, neurochemical altered response, and increased hippocampal synaptic transmission) were prevented by AT1-receptors blockade.
  
  
  CONCLUSIONS
  AT1-receptors are involved in the acute alterations and in the neuroadaptations induced by repeated amphetamine associated with neurocognitive processes.
authors.affiliation: Instituto de Farmacología Experimental Córdoba (IFEC-CONICET) Departamento de Farmacología, Facultad de Ciencias Químicas Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Natalia Andrea
authors.initials: NA
authors.lastname: Marchese
authors.affiliation: Instituto de Farmacología Experimental Córdoba (IFEC-CONICET) Departamento de Farmacología, Facultad de Ciencias Químicas Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Emilce
authors.initials: E
authors.lastname: Artur de laVillarmois
authors.affiliation: Instituto de Farmacología Experimental Córdoba (IFEC-CONICET) Departamento de Farmacología, Facultad de Ciencias Químicas Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Osvaldo Martin
authors.initials: OM
authors.lastname: Basmadjian
authors.affiliation: Instituto de Farmacología Experimental Córdoba (IFEC-CONICET) Departamento de Farmacología, Facultad de Ciencias Químicas Universidad Nacional de Córdoba, Córdoba, Argentina. mfperez@fcq.unc.edu.ar.
authors.forename: Mariela Fernanda
authors.initials: MF
authors.lastname: Perez
authors.affiliation: Laboratorio de Neurofarmacología, (IIBYT-CONICET), Universidad Nacional de Córdoba, Córdoba, Argentina.
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, Córdoba, Argentina.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bregonzio
mesh_terms: D000662:Amphetamines / Q000633:toxicity*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning; D001522:Behavior, Animal / Q000187:drug effects; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects; D007276:Injections, Intraventricular; D019808:Losartan / Q000494:pharmacology; D008297:Male; D057567:Memory, Long-Term / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D000662:Amphetamines; D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D000697:Central Nervous System Stimulants; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D019808:Losartan; C081643:candesartan
keywords: AT1 receptors; Amphetamine; Angiotensin II; Candesartan; FOS; Hippocampus; Inhibitory avoidance; Long-term memory; Long-term potentiation; Losartan