IIBYT   23944
INSTITUTO DE INVESTIGACIONES BIOLOGICAS Y TECNOLOGICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Brain Angiotensin II type 1 (AT1) receptors are involved in acute and long-lasting amphetamine-induced neurocognitive alterations
Autor/es:
MARCHESE, N.A.; ARTUR DE LA VILLARMOIS, E.; BASMADJIAN, O.M.; PEREZ. M.F.; BAIARDI, G.; BREGONZIO, C.
Lugar:
Rio de Janeiro
Reunión:
Congreso; 9º IBRO World Congress on Neuroscience; 2015
Institución organizadora:
International Brain Research Organization
Resumen:
Rationale: Angiotensin II (Ang II), by activation of its Brain Angiotensin Receptors type 1 (AT1), plays an active role as neuromodulator in the stress response and in dopamine (DA) release as well as in DA associated behaviors, including drug consumption, behavioral sensitization and learning and memory, among others. Likewise, psychostimulants drugs, such as amphetamine (Amph), are recognized for their mimetic activity over cathecholaminergic neurotransmission. Amph exposure can elicit different behavioral and cellular responses depending on the experimental administration protocol used. Moreover, altered responses can be observed after long withdrawal periods, when animals are re-exposed to the psychostimulant. Objectives: To assess the acute and long-term Amph-induced modifications in learning and memory and in cellular related events; and to evaluate the involvement of AT1 receptors in these events.Methods: male Wistar rats (250-300g) were used. To evaluate Amph acute effects, a single dose of Amph (0.5 or 2.5 mg/kg i.p.) was administered after post-training in the inhibitory avoidance test. To study the involvement of AT1 receptors in Amph acute effects, the AT1 receptor blocker Losartan was administered i.c.v. immediately before a single dose of Amph (0.5mg/kg i.p.). To evaluate the long?term Amph effects, the animals received a daily Amph (2.5 mg/kg, i.p.) injection for 5 days. The neuroadaptive changes were evidenced after 1 week of withdrawal with an Amph challenge dose (0.5 mg/kg i.p.). To study the participation of AT1 receptors in long?term Amph effects, the AT1 receptor blocker Candesartan (3mg/kg p.o.) was administered for 5 days prior to repeated Amph administration. In this case the inhibitory avoidance response, neuronal activation pattern and hippocampal synaptic transmission were evaluated.Results: The impairing effect in the passive avoidance response induced by post-training acute Amph administration was partially reverted by Losartan. The long-term changes induced by repeated Amph administration such as resistance to acute Amph interference in the inhibitory avoidance response, neurochemical altered response and increased hippocampal synaptic transmission were prevented by blockade of AT1 receptors previous to Amph administration.Conclusion: The AT1 receptors are involved in acute neurocognitive alterations as well as in the neuroadaptive changes induced by Amph associated with neurocognitive responses.