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

Previous results from our laboratory showed that angiotensin II AT(1) receptors (AT(1)-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 AT(1)-R activation in animals previously exposed to amphetamine. For this purpose male Wistar rats (250-320 g) were treated with amphetamine (2.5 mg/ 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 AT(1)-R in response to ANG II, induced by repeated amphetamine exposure. This functional AT(1)-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 AT(1)-R functionality should be considered among the psychostimulant-induced neuroadaptations. Published by Elsevier Ltd. on behalf of IBRO.