Brain AT1 Angiotensin II receptors involvement in the neurochemical long term effects induced by amphetamine.

PAZ MC; CABRERA RJ,; CANCELA LM; BREGONZIO C

Huerta Grande, Córdoba, Argentina

Congreso; First joint meeting of the argentine society for neurosciences (SAN) and the argentine workshop in neuroscience (TAN); 2009

SAN y TAN

The enhanced response to psychostimulants, termed behavioral sensitization, relies on time-dependent neuroplastic changes in the brain circuitry involved in motivational behavior. These changes are associated with the long-lasting hyper-reactivity of the mesolimbic dopaminergic pathway. It has been shown that a single exposure to amphetamine is sufficient to induce long-term behavioral, neurochemical and neuroendocrine sensitization in rats. The present study tested the hypothesis that Ang II AT1 receptors are involved in the neuroadaptative changes induced by a single exposure to amphetamine and that such changes are related to the development of behavioral and neurochemical sensitization. We studied the expression of neurochemical sensitization in Wistar male rats (250-280g) pretreated with an AT1 blocker, candesartan or vehicle (3 mg/kg p.o) for five days and after that injected once with amphetamine 5mg/kg i.p. The experiments were performed three weeks after amphetamine administration and the DA release from the nucleus accumbens core induced by amphetamine challenge was tested using in vivo microdialysis. In other group of animals the behavioral sensitization to D1 and D2 dopaminergic agonists was tested. In addition, in animals exposed to amphetamine it was determined the expression of AT1 receptors in relevant brain areas using immunohystochemistry. It was also tested the effect of AT1 blockade on the acute behavioral and neurochemical response to amphetamine. Our results suggests that AT1 blockade in some way affected the activity of the dopamine transporter or vesicular transporter that later resulted in a decrease of dopamine release in candesartanamphetamine pretreated animals. We also found that amphetamine exposure induce persistent changes in Ang II AT1 receptors in ventral and dorsal striatum and amygdala