AT1 Receptor as a Potential Target in Amphetamine-induced Neuro-inflammation

Abstract

Background: Amphetamines constitute a group of drugs associated with clinical use and illicit consumption. They induce dopamine neurotransmission and promote astrocyte reactivity and microglial activation events associated with their neurotoxic actions. The neuroinflammatory response induced by amphetamines occurs as a consequence of mechanisms that involve oxidative stress, glial reactivity and apoptosis. Brain angiotensin II, through its AT1 receptor (AT1-R), modulates dopaminergic, glutamatergic and GABAergic neurotransmission, which are involve in cognition, emotions and stress responses. AT1-R is present in neurons, astrocytes, microglia and endothelial cells having a key role in the development of an oxidative/inflammatory microenvironment. AT1-R promotes the initiation and progression of local brain inflammatory and oxidative responses under dopamine imbalance conditions. The available evidences support the protective effects of AT1-R blockade for the deleterious effects induced by amphetamine.Conclusion: The available evidences, together with the results obtained by our group, open the possibility to postulate AT1-R as a possible therapeutic target for neuroinflammatory responses associated with dopamine imbalanced related disorders.