Enhancement of thermal nociception and astrocyte reactivity in somatosensory cortex induced by anphetamine involves central AT1 receptor activation

BASMADJIAN, OM; BREGONZIO, C; LETICIA DELGADO MARÍN; PÉREZ, MF; OCCHIEPPO, VB; MARCHESE, NA; BAIARDI, G

Córdoba

Congreso; V Reunión Científica Anual del IIBYT; 2017

IIBYT (CONICET-UNC)

The use of psychostimulants, such as amphetamine (Amph), is associated with inflammatory processes over glia and vasculature. Brain Angiotensin II (Ang II), through AT1-receptors (AT1-R), modulates dopaminergic neurotransmission and plays a crucial role in inflammatory responses in brain vasculature and glia. Studies from our laboratory showed the involvement of AT1-Ron astrocyte reactivity and neuronal survival in the pre-limbic cortex after repeated exposure to Amph. Our aim for the present work was to extend the role of AT1-R in alterations induced by repeated exposure to Amph. Astrocyte reactivity, neuronal survival and brain microvascular network were analyzed at the somatosensory cortex. The thermal nociception was evaluated as a physiological outcome of this brain area. Male Wistar 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/kg i.p., day 6-10). On day 17, animals were sacrificed and the brains processed for immunohistochemistry against Von Willebrand factor and glial fibrillary acidic protein (G-FAP), and Nissl staining. Thermal nociception was evaluated using hot plate test on day 17 in another group of animals. Data were analyzed with two-way ANOVA followed by Bonferroni test. Our results indicate that Amph exposure induces an increase in occupied area by vessels and their tortuosity, astrocyte reactivity and neuronal apoptosis. Moreover, Amph exposure decreased the paw lick threshold behavior. Pretreatment with candesartan prevented the described alterations induced by psychostimulant. The Amph-induced structural changes at somatosensorial cortex, involving astrocytes, vasculature and neurons, implies AT1-R activation. The decreased thermal nociception and the structural changes could be considered as extended neuroadaptative responses to Amph.