4.5 Article

Neurovascular unit alteration in somatosensory cortex and enhancement of thermal nociception induced by amphetamine involves central AT1 receptor activation

Journal

EUROPEAN JOURNAL OF NEUROSCIENCE
Volume 45, Issue 12, Pages 1586-1593

Publisher

WILEY
DOI: 10.1111/ejn.13594

Keywords

angiotensin II; astrogliosis; candesartan; microvascular network; wistar male rats

Categories

Funding

  1. Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET) [11220090100852-KB1]
  2. Secretaria de Ciencia y Tecnica SECyT-UNC

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The use of psychostimulants, such as amphetamine (Amph), is associated with inflammatory processes, involving glia and vasculature alterations. Brain Angiotensin II (Ang II), through AT(1)-receptors (AT(1)-R), modulates neurotransmission and plays a crucial role in inflammatory responses in brain vasculature and glia. Our aim for the present work was to evaluate the role of AT(1)-R in long-term alterations induced by repeated exposure to Amph. Astrocyte reactivity, neuronal survival and brain microvascular network were analysed at the somatosensory cortex. Thermal nociception was evaluated as a physiological outcome of this brain area. Male Wistar rats (250-320g) were administered with AT(1)-R antagonist Candesartan/vehicle (3mg/kg p.o., days 1-5) and Amph/saline (2.5mg/kg i.p., days 6-10). The four experimental groups were: Veh-Sal, CV-Sal, Veh-Amph, CV-Amph. On day 17, the animals were sacrificed and their brains were processed for Nissl staining and immunohistochemistry against glial fibrillary acidic protein (GFAP) and von Willebrand factor. In another group of animals, thermal nociception was evaluated using hot plate test, in the four experimental groups, on day 17. Data were analysed with two-way anova followed by Bonferroni test. Our results indicate that Amph exposure induces an increase in: neuronal apoptosis, astrocyte reactivity and microvascular network, evaluated as an augmented occupied area by vessels, branching points and their tortuosity. Moreover, Amph exposure decreased the thermal nociception threshold. Pretreatment with the AT(1)-R blocker prevented the described alterations induced by this psychostimulant. The decreased thermal nociception and the structural changes in somatosensory cortex could be considered as extended neuroadaptative responses to Amph, involving AT(1)-R activation.

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