Enhancement of thermal nociception and astrocyte reactivity in somatosensorial cortex induced by amphetamine involves central AT1 receptor activation.

OCCHIEPPO, VICTORIA BELÉN; BASMADJIAN, OSVALDO MARTÍN; MARCHESE, NATALIA ANDREA; PEREZ MF; BREGONZIO C

Mar del Plata

Congreso; XLVIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE FARMACOLOGÍA EXPERIMENTAL (SAFE); 2016

SAIC SAFE SAI

The use of psychostimulants, such as amphetamine􀀊Amph􀀋, is associated 􀁙ith 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 􀀘􀀏􀀓􀀒􀀋. 􀀱n day 􀀓􀀙, animals 􀁙ere sacrificed and thebrains processed for immunohistochemistry against Von􀀹illebrand factor and glial fibrillary acidic protein 􀀊􀀩􀀏FA􀀲􀀋,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.