The neuroplastic changes induced by amphetamine involve the brain renin-angiotensin system (RAS).
Paz M.Constanza; Marchese Natalia; Imboden H.; Cancela Liliana M.; Bregonzio Claudia.
The enhanced response to psychostimulants relies on time-dependent neuroplastic changes involving long-lasting hyper-reactivity of dopaminergic pathways. A single exposure to amphetamine (AMPH) is sufficient to induce long-term changes in rats. Our study tested the hypothesis that Angiotensin II AT1 receptors are involved in the neuroadaptative changes induced by a single exposure to AMPH and that such changes are related to the development of neuroplasticity. Wistar male rats (250-300 g) were pretreated with an AT1 blocker, candesartan (3 mg/kg po) for five days and after that injected once with AMPH (5mg/kg ip). The Fos immunoreactive neurons (Fos-ir) in response to AMPH (0.5 mg/kg) were determined 3 weeks later. Other animals treated with AMPH (5mg/kg ip) were used 7 or 21 days later to determine the AT1 receptors expression by immunohystochemistry after AMPH (0.5 mg/kg) injection. Our results showed an increase in Fos-ir neurons in AMPH pretreated rats in NAcc and CPu and this response was prevented by the AT1 receptor blockade. AMPH produced an increase of AT1 receptors immunoreactivity in CPu and NAcc observed 7 and 21 days after treatment. The brain RAS should be considered for a better understanding of the mechanisms involved in psychostimulants-induced neuroplasticity.
