A PREVIOUS HISTORY OF REPEATED AMPHETAMINE EXPOSURE MODIFIES BRAIN ANGIOTENSIN II AT1 RECEPTOR FUNCTIONALITY

CASARSA, B.S.; MARINZALDA, M.;; MARCHESE, N.A; PAZ, M C; VIVAS, L.; BAIARDI, G.;; BREGONZIO, C.

NEUROSCIENCE

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2015 vol. 307 p. 1 - 13

0306-4522

Abstract?Previous results from our laboratory showed thatangiotensin II AT1 receptors (AT1-R) are involved in the neuroadaptativechanges induced by amphetamine. The aim ofthe present work was to study functional and neurochemicalresponses to angiotensin II (ANG II) mediated by AT1-R activationin animals previously exposed to amphetamine. Forthis purpose male Wistar rats (250?320 g) were treated withamphetamine (2.5 mg/kg/day intraperitoneal) or saline for5 days and implanted with intracerebroventricular (i.c.v.)cannulae. Seven days after the last amphetamine administrationthe animals received ANG II (400 pmol) i.c.v. Onegroup 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 electrolytesand plasma renin activity determination and then they weresacrificed for Fos-IR determination in Oxytocinergic neurons(Fos-OT-IR). Results: Repeated amphetamine exposure(a) prevented the increase in sodium intake and Fos-IR cellsin caudate-putamen and accumbens nucleus induced byANG II i.c.v. (b) potentiated urinary sodium excretion andFos-OT-IR in hypothalamus and (c) increased the inhibitoryresponse in plasma renin activity, in response to ANG II i.c.v.Our results indicate a possible functional desensitisation ofAT1-R in response to ANG II, induced by repeated amphetamineexposure. This functional AT1-R desensitisation allowsto unmask the effects of ANG II i.c.v. mediated by oxytocin.We conclude that the long lasting changes in brainAT1-R functionality should be considered among thepsychostimulant-induced neuroadaptations.