ENHANCEMENT OF THERMAL NOCICEPTION AND ASTROCYTE REACTIVITY IN SOMATOSENSORIAL CORTEX INDUCED BY AMPHETAMINE INVOLVES CENTRAL AT1 RECEPTOR ACTIVATION

VICTORIA B OCCHIEPPO; OSVALDO M BASMADJIAN; NATALIA A. MARCHESE; PÉREZ MARIELA F.; CLAUDIA BREGONZIO

Mar del Plata

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC) LXIV REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI) XLVIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE FARMACOLOGÍA EXPERIMENTAL (SAFE); 2016

SAFE SAIC SAI

The use of psychostimulants, such as amphetamineAmph, is associated Yith inflammatory processes over gliaand vasculature. Brain Angiotensin II (Ang II), through AT1-receptors (AT1-R), modulates dopaminergic neurotransmissionand plays a crucial role in inflammatory responsesin brain vasculature and glia. Studies from our laboratoryshowed the involvement of AT1-R on astrocyte reactivityand neuronal survival in the pre-limbic cortex after repeatedexposure to Amph. Our aim for the present work was toextend the role of AT1-R in alterations induced by repeatedexposure to Amph. Astrocyte reactivity, neuronal survivaland brain microvascular network were analyzed at thesomatosensory cortex. The thermal nociception was evaluatedas a physiological outcome of this brain area. MaleWistar rats (250-320g), at standard laboratory conditions,were administered with AT1-R antagonist Candesartan/vehicle (3 mg/kg p.o., day 1-5) and Amph/saline (2.5 mg/kgi.p., day . 1n day , animals Yere sacrificed and thebrains processed for immunohistochemistry against Von9illebrand factor and glial fibrillary acidic protein )FA2,and Nissl staining. Thermal nociception was evaluatedusing hot plate test on day 17 in another group of animals.Data were analyzed with two-way ANOVA followed byBonferroni test. Our results indicate that Amph exposureinduces an increase in: occupied area by vessels and theirtortuosity, astrocyte reactivity and neuronal apoptosis.Moreover, Amph exposure decreased the paw lick thresholdbehavior. Pretreatment with candesartan preventedthe described alterations induced by psychostimulant. TheAmph-induced structural changes at somatosensorial cortex,involving astrocytes, vasculature and neurons, impliesAT1-R activation. The decreased thermal nociception andthe structural changes could be considered as extendedneuroadaptative responses to Amph.