The extent of neuroadaptive responses to psychostimulants: Focus on brain Angiotensin system

Abstract

Amphetamine and cocaine are drugs of abuse worldwide consumed for their stimulant properties in the central nervous system. They mainly potentiate noradrenergic and dopaminergic neurotransmission and induce long-term changes in multiple neuronal circuits, modifying the future responses to pharmacological or non-pharmacological challenges. The altered neuronal connectivity induced by psychostimulants has 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-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 functionality of AT1 receptors after amphetamine exposure. The evidence presented in this chapter highlight the RAS as a neuromodulatory system of superior brain activities, and further validate Angiotensin II involvement in amphetamine-induced alterations through AT1 receptor activation. The AT1 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.