How deep amphetamine impacts our brain and why to focus on Angiotensin II

Abstract

Amphetamine is known for its stimulant effect over the central nervous system exerted mainly through noradrenergic and dopaminergic neurotransmissions. However, this psychostimulant induces long-term changes in multiple neuronal circuits, modifying their future responses to pharmacological or non-pharmacological challenges. Accumulated evidence regarding neuronal altered connectivity in brain areas processing reward, cognition and decision making, support its use in experimental conditions in order to learn about mental disorders. For this reason, amphetamine exposure is validated as a pharmacological tool to resemble several psychiatric diseases, such as the dopaminergic/ glutamatergic imbalance in schizophrenia and mania. Moreover, its effects extend beyond neurotransmission, as the exposure to this psychostimulant has been associated to brain vascular damage and neuroinflammation. Remarkably, brain angiotensin II, through angiotensin type 1 receptors (AT1-R), modulates dopaminergic and glutamatergic neurotransmission - among others -, and also it is involved in neurovascular and inflammatory responses. Our research explored the neuroadaptative responses and neuroinflammation evoked by the psychostimulant and depending on AT1-R that might resemble some features linked to different brain disorders. In this chapter we will present data showing the reciprocity between brain angiotensin II system and amphetamine exposure in the development and expression of behavioral, neurochemical and glial alterations.