title: A previous history of repeated amphetamine exposure modifies brain angiotensin II AT1 receptor functionality.
abstract: Previous results from our laboratory showed that angiotensin II AT1 receptors (AT1-R) are involved in the neuroadaptative changes induced by amphetamine. The aim of the present work was to study functional and neurochemical responses to angiotensin II (ANG II) mediated by AT1-R activation in animals previously exposed to amphetamine. For this purpose male Wistar rats (250-320 g) were treated with amphetamine (2.5mg/kg/day intraperitoneal) or saline for 5 days and implanted with intracerebroventricular (i.c.v.) cannulae. Seven days after the last amphetamine administration the animals received ANG II (400 pmol) i.c.v. One group was tested in a free choice paradigm for sodium (2% NaCl) and water intake and sacrificed for Fos immunoreactivity (Fos-IR) determinations. In a second group of rats, urine and plasma samples were collected for electrolytes and plasma renin activity determination and then they were sacrificed for Fos-IR determination in Oxytocinergic neurons (Fos-OT-IR).
  
  
  RESULTS
  Repeated amphetamine exposure (a) prevented the increase in sodium intake and Fos-IR cells in caudate-putamen and accumbens nucleus induced by ANG II i.c.v. (b) potentiated urinary sodium excretion and Fos-OT-IR in hypothalamus and (c) increased the inhibitory response in plasma renin activity, in response to ANG II i.c.v. Our results indicate a possible functional desensitisation of AT1-R in response to ANG II, induced by repeated amphetamine exposure. This functional AT1-R desensitisation allows to unmask the effects of ANG II i.c.v. mediated by oxytocin. We conclude that the long lasting changes in brain AT1-R functionality should be considered among the psychostimulant-induced neuroadaptations.
authors: Laboratorio de Neurofarmacología, Instituto de Investigaciones Biológicas y Tecnológicas (IIByT-CONICET), Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Universidad Católica de Córdoba, Córdoba, Argentina.
authors: B S
authors: BS
authors: Casarsa
authors: Laboratorio de Neurofarmacología, Instituto de Investigaciones Biológicas y Tecnológicas (IIByT-CONICET), Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Universidad Católica de Córdoba, Córdoba, Argentina.
authors: M Á
authors: MÁ
authors: Marinzalda
authors: Instituto de Farmacología Experimental Córdoba (IFEC-CONICET), Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors: N A
authors: NA
authors: Marchese
authors: Instituto de Farmacología Experimental Córdoba (IFEC-CONICET), Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors: M C
authors: MC
authors: Paz
authors: Instituto de Investigación Médica Mercedes y Martín Ferreyra (INIMEC-CONICET), Universidad Nacional de Córdoba, Córdoba, Argentina.
authors: L
authors: L
authors: Vivas
authors: Laboratorio de Neurofarmacología, Instituto de Investigaciones Biológicas y Tecnológicas (IIByT-CONICET), Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Universidad Católica de Córdoba, Córdoba, Argentina.
authors: G
authors: G
authors: Baiardi
authors: Instituto de Farmacología Experimental Córdoba (IFEC-CONICET), Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina. Electronic address: bregonzio@fcq.unc.edu.ar.
authors: C
authors: C
authors: Bregonzio
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004326:Drinking / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D010121:Oxytocin / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism
chemical_list: C524087:Agtrap protein, rat; D000697:Central Nervous System Stimulants; D016761:Oncogene Proteins v-fos; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D010121:Oxytocin; D012964:Sodium; D000661:Amphetamine; D005947:Glucose
keywords: AT(1) receptors; amphetamine; angiotensin II; natriuresis; oxytocin; sodium intake