The extent of neuroadaptive responses to psychostimulants: focus on brain angiotensin system

BREGONZIO, C; MARCHESE, NA; PAZ, MC; ARTUR DE VILLAMOIRS, E; BAIARDI, G; PEREZ, MF

Psychiatry and Neuroscience Update - Vol. II: A Translational Approach

Springer

Lugar: Berlín, Heidelberg; Año: 2016;

Amphetamine and cocaine are drugs of abuse worldwide consumed for their stimulant properties over the central nervous system. They mainly potentiate noradrenergic and dopaminergic neurotransmission and induce long-term changes in multiple neuronal circuits, modifying their future responses to pharmacological or non-pharmacological challenges. The altered neuronal connectivity induced by psychostimulants has been long studied in reward processing brain areas and in behavioral performance. 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 innervated areas 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 renin angiotensin system (RAS) and in the AT1 receptors functionality after amphetamine exposure.The evidences presented in this chapter stand out the RAS as a neuromodulatory system of superior brain activities, and further validate the Angiotensin II involvement in amphetamine-induced alterations by activating AT1 receptors. The AT1receptors blockers are currently and safety 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