Angiotensin II AT1 Receptors Are Involved in Neuronal Activation Induced by Amphetamine in a Two-Injection Protocol

• Published in: BioMed research international Vol. 2013; no. 2013; pp. 1 - 10
• Main Authors: Bregonzio, Claudia, Cancela, Liliana M., Marchese, Natalia Andrea, Paz, Maria Constanza
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2013
• Subjects: Amphetamine - administration & dosage; Animals; Behavior, Animal - drug effects; Benzimidazoles - administration & dosage; Brain Mapping; Immunohistochemistry; Neurons - metabolism; Neurons - ultrastructure; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Proto-Oncogene Proteins c-fos - isolation & purification; Proto-Oncogene Proteins c-fos - metabolism; Rats; Receptor, Angiotensin, Type 1 - isolation & purification; Receptor, Angiotensin, Type 1 - metabolism; Tetrazoles - administration & dosage; Ventral Tegmental Area - drug effects; Ventral Tegmental Area - metabolism
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2013/534817

It was already found that Ang II AT1 receptors are involved in the neuroadaptative changes induced by a single exposure to amphetamine, and such changes are related to the development of behavioral and neurochemical sensitization. The induction of the immediately early gene c-fos has been used to define brain activated areas by amphetamine. Our aim was to evaluate the participation of AT1 receptors in the neuronal activation induced by amphetamine sensitization. The study examined the c-fos expression in mesocorticolimbic areas induced by amphetamine challenge (0.5 mg/kg i.p) in animals pretreated with candesartan, a selective AT1 receptor blocker (3 mg/kg p.o × 5 days), and amphetamine (5 mg/kg i.p) 3 weeks before the challenge. Increased c-fos immunoreactivity was found in response to the amphetamine challenge in the dorsomedial caudate-putamen and nucleus accumbens, and both responses were blunted by the AT1 receptor blocker pretreatment. In the infralimbic prefrontal cortex, increased c-fos immunoreactivity was found in response to amphetamine and saline challenge, and both were prevented by the AT1 receptor blocker. No differences were found neither in ventral tegmental area nor prelimbic cortex between groups. Our results indicate an important role for brain Ang II in the behavioral and neuronal sensitization induced by amphetamine.