LONG-LASTING AMPHETAMINE EFFECTS OVER CENTRAL ANGIOTENSIN II RESPONSES INVOLVE AT1-R

PIERMARINI, MARIA JOSEFINA; OCCHIEPPO, VICTORIA BELEN; BASMADJIAN, OSVALDO MARTIN; BAIARDI GUSTAVO; BREGONZIO, CLAUDIA

Congreso; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2023

in regulating the sympathetic and neuroendocrine systems throughthe activation of AT1 receptors (AT1-R). Studies on mammals haveshown that administering Ang II through the intracerebroventricular(i.c.v) route increases water and sodium intake, as well as renalsodium excretion. Our group’s previous findings have shown thatAT1-R are involved in behavioural and neurochemical sensitizationinduced by amphetamine (Amph) administration. Our current aim isto assess the functional and neurochemical response to Ang II, viathe AT1-R activation, in animals that have been previously exposedto Amph. Male Wistar rats (250-320g) were injected intraperitoneallywith Amph (2.5mg/kg/day) or saline for 5 days, and implanted withi.c.v. cannulae. Twenty-one days after the last Amph administration,the animals received Ang II (400pmol) i.c.v. First group: the animalswere tested in a free choice paradigm for sodium (2% NaCl) and waterintake, and sacrificed for Fos immunoreactivity determinations.Second group: urine and plasma samples were collected for electrolytesand plasma renin activity determination. Third group, theanimals were tested in the plus maze or the holeboard for anxietyand memory work evaluation, respectively. Previous Amph exposurealtered the physiological and behavioral responses describedfor central Ang II administration. Remarkably, the AT1-R blockadeprevented most of these alterations but anxiety. Our results highlightthat repeated Amph exposure attenuates the AT1-R functionality in along-lasting manner, modifying the brain Ang II-induced responses.