Amphetamine-induced sensitization as an animal model of schizophrenia: Behavioral characterization and role of angiotensin II AT1 receptors

BASMADJIAN, OSVALDO MARTIN; OCCHIEPPO, VICTORIA BELÉN; MARCHESE, NATALIA ANDREA; BAIARDI, GUSTAVO; BREGONZIO, CLAUDIA

Mar del Plata

Congreso; LX Reunión de la Sociedad Argentina de Investigación Clínica (SAIC), LXIV Reunión Anual de la Sociedad Argentina de Inmunología(SAI) y XLVIII Reunión Científica anual de la Sociedad Argentina de Farmacología Experimental (SAFE); 2016

Sociedad Argentina de Investigación Clínica (SAIC), Sociedad Argentina de Inmunología(SAI) y Sociedad Argentina de Farmacología Experimental (SAFE)

Amphetamine (amph) exposure induces adaptive responsesobserved as increased dopaminergic reactivity in mesolimbic pathway concomitant with decreased dopaminergic reactivity in themesocortical one. Similar alterations have been described in thepathology of schizophrenia. Forthis reason, amph-induced sensitization is a validated animal model of schizophrenia;resemblingdescribed positive signs and cognitive defcits. Brain AngiotensinII,through AT1 receptors (AT1-R), modulates dopaminergicneurotransmission in limbic areas. Previously, we found that behavioralneuroadaptativeresponses to amph involved AT1-R activation.The aim for the presentwork was to study AT1-R involvementin behavioral responses in an animal model of schizophreniausing amph-induced sensitization. Male Wistar rats (250-320g),at standard laboratory conditions, were administered with AT1-Rantagonist Candesartan/vehicle (3 mg/kg p.o., day 1-10) andamph/saline (2.5mg/kg i.p., day 6-10). On day 31 we evaluatedthe locomotor sensitized response to saline/amph challenge (0.5mg/kg i.p.) and the working memory (Y-maze test).Data wereanalyzed with two-way ANOVA followed by Bonferroni test andt-test. We corroborated that the amph protocol used inducesbehavioral sensitization to amphchallenge and cognitive defcit,observed as a decreased spontaneous alternations in the Y-maze.Moreover, it was found an increased susceptibility to stress, expressed as augmented locomotor activity, 30 minutes after salineinjection. So, we conclude that this protocol was effective to elicitsome of the described signs of schizophrenia. Interestingly, theAT1-Rantagonist blunted the neuroadaptative responses to thepsychostimulant. Since the available therapeutic treatments havelow effcacy and high incidence of side-effects, new pharmacological approaches become necessary. However, further studiesare needed to postulate the AT1-R antagonists as an alternativepharmacological tool.