The Extent of Neuroadaptive Responses to Psychostimulants: Focus on Brain Angiotensin System

PÉREZ, M.F.; PAZ, M.C.; ARTUR DE LA VILLARMOIS, E.; BREGONZIO, C.; BAIARDI, G; MARCHESE, N.A.

Psychiatry and Neuroscience Update: A Translational Approach

Springer International Publishing

Año: 2017; p. 193 - 204

Amphetamine and cocaine are drugs of abuse worldwide consumed fortheir stimulant properties in the central nervous system. They mainlypotentiate noradrenergic and dopaminergic neurotransmission and inducelong-term changes in multiple neuronal circuits, modifying the future responses of the latter to pharmacological or non-pharmacological challenges.The altered neuronal connectivity induced by psychostimulantshas long been studied in reward processing brain areas and in behavioral responses. Different neurotransmitter systems are involved in these responses, including the neuropeptide angiotensin II. Locally produced brain angiotensin II, acting through AT1 receptors, plays an important role in the modulation of central dopaminergic neurotransmission. Dopamine-innervatedareas such as caudate putamen, nucleus accumbens, substantianigra, hypothalamus, and ventral pallidum express high AT1 receptordensity. Our recent studies show the role of angiotensin II AT1 receptors inthe development of neuroadaptative behavioral and neurochemicalchanges induced by amphetamine. Moreover, we found alterations in thecomponents of the renin angiotensin system (RAS) and in the functionalityof AT1 receptors after amphetamine exposure. The evidence presentedin this chapter highlight the RAS as a neuromodulatory system of superiorbrain activities, and further validate Angiotensin II involvement inamphetamine-induced alterations through AT1 receptor activation. TheAT1 receptor blockers are currently and safely used in clinic for different pathologies, so they would be prominent candidates for pharmacological treatment in pathologies related to altered dopamine neurotransmission,such as drug addiction, schizophrenia, or even depression.