Angiotensin II AT1 receptors mediate neuronal sensitization and sustained blood pressure response induced by a single injection of amphetamine

MARCHESE, NATALIA ANDREA; PAZ MC; CAEIRO X; DADAM MF; BAIARDI, G; PEREZ MF; BREGONZIO C

Mar del Plata

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2016

SAIC SAFE SAI

A single exposure to amphetamine induces neurochemicalsensitization in striatal areas. The neuropeptide angiotensin II,through AT1 receptors (AT1-R) activation, is involved in theseresponses. Ho􀁙ever, amphetamine􀀏induced alterations can beextended to extra􀀏striatal areas involved in blood pressure con troland their physiological outcomes. 􀀱ur aim for the present study􀁙as to analyze the possible role for AT1-R in these events usinga t􀁙o􀀏injection protocol and to further characterize the proposedAT1-R antagonism protocol.Central effect of orally administered AT1-R blocker (Candesartan,􀀕mg/􀁍g p.o. 􀂪 􀀗 days􀀋 􀁙as analyzed recording spontaneusactivity of neurons 􀁙ithin locus coeruleus. 􀀫n another group ofanimals, pretreated 􀁙ith AT1-R blocker or vehicle, sensitization􀁙as achieved by a single administration of amphetamine 􀀊􀀗mg/􀁍g i.p.􀀏 day 􀀘􀀋 follo􀁙ed by a 􀀕􀁙ee􀁍 period off drug. After receivingan amphetamine challenge 􀀊􀀒.􀀗mg/􀁍g i.p.􀀋,􀁙e evaluated􀀜 􀀓􀀋the sensitized c􀀏Fos expression in locus coeruleus 􀀊LC􀀋,nucleusof the solitary tract 􀀊􀀰TS􀀋, caudal ventrolateral medulla 􀀊A􀀓􀀋 andcentral amygdala 􀀊CeAmy􀀋􀀝 and 􀀔􀀋 the blood pressor response.AT1􀀏􀀴bloc􀁍ade decreased LC neurons􀅏 spontaneous firing rate.􀀯oreover, sensitizedc􀀏Fos immunoreactivity 􀁙as found in LCand 􀀰TS􀀝 and both responses 􀁙ere blunted by the AT1-R blockerpretreatment. 􀀯ean􀁙hile, no differences 􀁙ere found neither inCeAmy nor A􀀓. Sensitized pressor response 􀁙as observed assustained changes in mean arterial pressure and 􀁙as effectivelyprevented by AT1-R blockade.