Brain renin-angiotensin system: A novel therapeutic target for psychostimulant and alcohol related disorders?

Abstract

The renin angiotensin system (RAS) is involved not only in the regulation of blood pressure and fluid homeostasis, but also in the modulation of multiple additional functions in the brain. In these sense, it was found to be involved in many neuroadaptive responses induced by drugs of abuse such as cocaine, amphetamine, alcohol, among others.It is extensively known that the dopaminergic neurotransmission in the nucleus accumbens and caudate-putamen plays a critical role in the rewarding effects of psychostimulant drugs and alcohol. The main and more studied actions of RAS are mediated by the neuropeptide Angiotensin II (Ang II) that belongs to the group of peptides known to stimulate dopamine release. There is growing evidence showing a key role of RAS in the development of neuroadaptive changes related to behavioral sensitization induced by natural reinforces and drugs of abuse. Recently, we found evidence involving the AT1 receptors in the neuroadaptive changes induced by amphetamine. Moreover, others found evidence that Ang II AT1 receptors are strongly involved in ethanol intake in rodents. Our aim is to present and discuss the evidence supporting an important role of brain RAS in neuroadaptive responses induced by two of the most abused drugs: amphetamine and alcohol, proposing this system as a potential therapeutic target in the treatment of disorders related to these drugs of abuse.