Long-lasting amphetamine effects over cebtral Angiotensin II responses involve AT1-R

Abstract

Angiotensin II (Ang II), a pleiotropic neuropeptide, plays a critical role in regulating the sympathetic and neuroendocrine systems through the activation of AT 1 receptors (AT1-R). Studies on mammals have shown that administering Ang II through the intracerebroventricular (i.c.v) route increases water and sodium intake, as well as renal sodium excretion. Our group’s previous findings have shown that AT 1-R are involved in behavioural and neurochemical sensitization induced by amphetamine (Amph) administration. Our current aim is to assess the functional and neurochemical response to Ang II, via the AT 1-R activation, in animals that have been previously exposed to Amph. Male Wistar rats (250-320g) were injected intraperitoneally with Amph (2.5mg/kg/day) or saline for 5 days, and implanted with i.c.v. cannulae. Twenty-one days after the last Amph administration, the animals received Ang II (400pmol) i.c.v. First group: the animals were tested in a free choice paradigm for sodium (2% NaCl) and water intake, and sacrificed for Fos immunoreactivity determinations. Second group: urine and plasma samples were collected for electrolytes and plasma renin activity determination. Third group, the animals were tested in the plus maze or the holeboard for anxiety and memory work evaluation, respectively. Previous Amph exposure altered the physiological and behavioral responses described for central Ang II administration. Remarkably, the AT1-R blockade prevented most of these alterations but anxiety. Our results highlight that repeated Amph exposure attenuates the AT1-R functionality in a long-lasting manner, modifying the brain Ang II-induced responses.