Monitoring dopamine in the mesocorticolimbic and nigrostriatal systems by microdialysis : relevance for mood disorders and Parkinson’s disease

Abstract

Dopamine (DA) is a versatile neurotransmitter that has a fundamental role in almost all behavioral aspects, from motor control to mood regulation, cognition, drug addiction, and reward. For this reason the pathophysiology of DAergic systems is one of the most investigated topics in neuroscience. Dopamine pathways in the brain are generally divided into the well-characterized mesostriatal (nigrostriatal) system, which originates in the substantia nigra pars compacta (SNc) and projects to the dorsal striatum, and the mesocorticolimbic system, which starts in the ventral tegmental area (VTA) and projects to the frontal cortex and limbic areas, including the amygdala and the nucleus accumbens. Degeneration of the nigrostriatal neurons results in the motor defi cits of Parkinson ’ s disease (PD), whereas dysfunction of the mesocorticolimbic system leads to various mood disorders, including depression, schizophrenia, and drug abuse. These neuropsychiatric diseases are in reality multifactorial disorders, and other neurotransmitter dysfunction is likely to occur. Serotonin (5 - HT) - containing neurons originating from the medial and dorsal raphe nuclei innervate both the substantia nigra and the VTA. In addition, terminal areas of the SNc and VTA receive input from 5 - HT – ergic neurons originating in the raphe nuclei. Thus, at the neuroanatomical levelsthere is a close relationship between 5 - HT and DA - containing neurons, and this suggests that 5 - HT could regulate the function of DA neurons via actions on midbrain DA cell bodies and on DA terminals. Microdialysis, coupled to high - performance liquid chromatography (HPLC), is an established technique for studying physiological, pharmacological, and pathological changes of a wide range of low - molecular - weight substances in the brain extracellular fluid. It is based on the evidence that a probe made of a hollow fiber permeable to solutes of low molecular weight inserted into the brain tissue mimics blood capillaries in exchanging material from and to the extracellular fluid. Microdialysis has been employed over the last 25 years by several authors, primarily to study brain function and changes in levels of endogenous compounds such as neurotransmitters or metabolites. Nevertheless, in central nervous system studies, reverse microdialysis has been used extensively for the study of the effects of diverse pharmacological and toxicological agents, such as antidepressants, antipsychotics, antiparkinsonians, hallucinogens, drugs of abuse, and experimental drugs, on local effects on neurotransmission at different central nuclei. Thus, the microdialysis approach has contributed largely not only to clarification of the physiological role of the serotonergic and dopaminergic neuronal systems but also to the development of therapeutic strategies for the treatment of a number of neuropsychiatric disorders. In this chapter we therefore focus on the microdialysis studies that have extensively explored the role of DA central systems in the pathophysiology of the main neuropsychiatric disorders.