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

ARTUR DE LA VILLARMOIS E; PEREZ MF; BREGONZIO C; PAZ MC; BAIARDI, G; MARCHESE, NATALIA ANDREA

Psychiatry and Neuroscience Update

Springer

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 futureresponses to pharmacological or non-pharmacological challenges. Thealtered neuronal connectivity induced by psychostimulants has long beenstudied in reward processing brain areas and in behavioral responses.Different neurotransmitter systems are involved in these responses, includingthe neuropeptide angiotensin II. Locally produced brain angiotensin II,acting through AT1 receptors, plays an important role in the modulation ofcentral dopaminergic neurotransmission. Dopamine-innervatedareas such as caudate putamen, nucleus accumbens, substantia nigra, hypothalamus, and ventral pallidum express high AT1 receptor density.Our recent studies show the role of angiotensin II AT1 receptors in the development of neuroadaptative behavioral and neurochemical changes induced by amphetamine. Moreover, we found alterations in the components of the reninangiotensin system (RAS) and in the functionality of AT1 receptors afteramphetamine exposure. The evidence presented in this chapter highlightthe RAS as a neuromodulatory system of superior brain activities, andfurther validate Angiotensin II involvement in amphetamine-inducedalterations through AT1 receptor activation. The AT1 receptor blockers arecurrently and safely used in clinic for different pathologies, so they would be prominent candidates for pharmacological treatment in pathologiesrelated to altered dopamine neurotransmission, such as drug addiction,schizophrenia, or even depression.