Renin-angiotensin sistem modulating funtions in the cpu
Marinzalda, M. A
Paz, María Constanza
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The caudate-putamen (CPu) of the striatum is one of the main entrances to the basal ganglia. The CPu is fundamentally a dopaminergic area receiving dopamine innervation from the substantia nigra, ventral tegmental area, and mesencephalic structures, but also has noradrenergic inputs from a post-encephalic area, the locus coeruleus, and glutamatergic innervation from cortical structures and cholinergic and GABAergic interneurons. It is well known that functional interactions between different neurotransmission systems play a crucial integrative role in the caudate-putamen, and are widely recognized as contributing to central motor activity and movements, and also to the processing of cognitive and limbic functions, despite autonomic responses across the noradrenergic system. Not only does typical neurotransmission regulate these functions, but peptidergic systems also have an important role. The brain renin-angiotensin system (RAS) is involved not only in the regulation of blood pressure, but also in the modulation of multiple additional functions in the brain, including processes of sensory information, learning and memory, and the regulation of emotional and behavioral responses. There is increasing ontogenetic, anatomic and functional evidence of the existence of a brain renin-angiotensin system and of its interaction with other putative neurotransmitters and their receptors. All components of the RAS have been observed in the striatum, and Ang II modulates dopamine release from striatal dopaminergic terminals, in vivo and in vitro, via their AT1 receptors. There is considerable evidence supporting a key role for dopamine (DA) neurotransmission in the Cpu in long-term neuroadaptative changes induced by stress or psychostimulants, such as cocaine or amphetamine. Repeated amphetamine or cocaine administration results in progressive and enduring enhancement of their psychomotor and positive reinforcing effects (sensitization phenomenon). We recently found evidence of the participation of Ang II, through its AT1 receptors, in the development of the locomotor sensitization induced by psychostimulant drugs. Moreover, the brain RAS may play a role in the pathogenesis and progression of Parkinson?s disease and aging-related loss of DA neurons. Manipulation of RAS components may be useful for neuroprotection in Parkinson?s disease patients because local RAS plays a major role in proinflammatory and pro-oxidative changes in aged substantia nigra. RAS is involved in modulating neurotransmission systems in the CPu and their functions, and for this reason it could be a possible target in the treatment of stress related diseases, drug abuse or neurodegenerative disorders.