Amphetamine induced differential effects in vascular and glial components at somatosensory cortex: Why to focus on AT1 receptors

Abstract

Amphetamine (Amph), is associated with inflammatory processes, involving glial and vascular alterations. Brain Angiotensin II, through AT1-receptors (AT1-R), modulates dopaminergic neurotransmission and plays a crucial role in inflammatory responses. Our aim was to evaluate the role of AT1-R in long-term alterations induced by repeated exposure to Amph. Astrocyte and microglia reactivity, and brain microvascular network were analysed at the somatosensory cortex (S1 Barrel and S1 Trunk area). Male Wistar rats (250–320 g) were administered with AT1-R antagonist Candesartan/vehicle (3 mg/kg p.o., days 1–10) and Amph/saline (2.5 mg/kg i.p., days 6–10). The four experimental groups at the two times evaluated (17 and 31 days) were: Veh-Sal, CV-Sal, Veh-Amph, CV-Amph. On days 17 and 31 the animals were sacrificed and their brains were processed for immunohistochemistry against GFAP (astroglial marker), CD11b (microglial marker) and von Willebrand factor (vascular marker). Data were analysed with factorial ANOVA followed by Bonferroni test. Our results indicate that Amph exposure induces an endurable increase in astrocyte and microglia reactivity at S1 Barrel and S1 Trunk area. Although, the microvascular rearrangement (evaluated as vascular area density, branching points and tortuosity) showed time dependant differential response to Amph, since at day 31 these parameters return to basal conditions at S1 Barrel. Meanwhile, at S1 Trunk the vascular changes were observed only at day 31. Pretreatment with the AT1-R blocker prevented the described alterations induced by Amph. We conclude that neuroplastic changes induced by Amph demand an AT1-R active role showing a regional susceptibility at vascular level.Fil: Armonelli Fiedler, Samanta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Occhieppo, Victoria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Basmadjian, Osvaldo Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Bregonzio Diaz, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Baiardi, Gustavo Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaReunión anual de sociedades de BiocienciaMar del PlataArgentinaSociedad Argentina de Investigación ClínicaAsociación Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaSociedad Argentina de ProtozoologíaAsociación Argentina de NanomedicinasAsociación Argentina de Ciencia y Tecnología de Animales de Laboratori

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