IFEC   20925
INSTITUTO DE FARMACOLOGIA EXPERIMENTAL DE CORDOBA
Unidad Ejecutora - UE
artículos
Título:
Brain Angiotensin II AT1 receptors are involved in the acute and long-term amphetamine-induced neurocognitive alterations
Autor/es:
MARCHESE, N; ARTUR DE LA VILLARMOIS, E; BASMADJIAN, OM; PÉREZ, MF; BAIARDI, G; BREGONZIO C
Revista:
PSYCHOPHARMACOLOGY
Editorial:
SPRINGER
Referencias:
Lugar: Berlin; Año: 2015 vol. 233 p. 795 - 807
ISSN:
0033-3158
Resumen:
Rationale.Angiotensin II, by activation of its brain AT1 receptors (AT1-R), plays an active role as neuromodulator in DA transmission.DA is involved in cognitive processes and brain related areas connectivity. Amphetamine (Amph) by its mimetic activity over DA neurotransmission elicits altered responsesafter long-term withdrawal periods, when animals are re-exposed to the drug. AT1-R play an active role in the development of dopaminergic and behavioral sensitization induced by Amph.Objective.Assessthe acute and long-term Amph-induced alterationsin long-term memoryandin cellular related eventsandevaluatethe AT1-R involvement in these events.Methods.Male Wistar rats (250-300g). Acute effects: Amph (0.5/2.5 mg/kg i.p.) was administered after post-training inthe inhibitory avoidance (IA) response. The AT1-R blocker Losartan was administered i.c.v. before a single dose of Amph (0.5mg/kg i.p.). Long-term effects:The AT1-R blocker Candesartan (3mg/kg p.o.) was administered for 5 days followed by 5 consecutive days ofAmph (2.5 mg/kg/day, i.p.). The neuroadaptive changes were evidenced after 1 week of withdrawal with an Amph challenge(0.5 mg/kg i.p.). The IA response, the neuronal activation pattern and the hippocampal synaptic transmission were evaluated.Results.The impairing effect in the IA response of post-training acute Amph was partially prevented by Losartan. The long-term changes induced by repeated Amph (resistance to acute Amph interference in the IA response, neurochemical altered response and increased hippocampal synaptic transmission) were prevented by AT1-R blockade.Conclusions.AT1-R are involved inthe acute alterations and in the neuroadaptations induced by repeated Amph associated with neurocognitive processes.