Dopamine function

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Dopamine function

Dopamine (DA) is a monoamine neurotransmitter of both central and peripheral nervous system. It deserves special attention because of its involvement in a very diverse and very basic set of functions, including motor behavior, cognition and emotional states. When things go wrong with the dopamine system, the consequences for the body and the brain are severe – they include Parkinson’s disease, Huntington’s chorea, tardive dyskinesia, and schizophrenia. Many drugs associated with addictive behavior, such as amphetamines and cocaine, act through dopaminergic neurons. Dopamine acts through G-protein coupled receptors, and its most common action is to change the rate of cAMP production, either upwards or downwards. The complications arise because cAMP participates in a wide variety of cellular mechanisms and because cells respond to multiple neurotransmitters and neuromodulators whose actions overlap in time and space.

The precursor for the synthesis of DA is the aromatic amino acid tyrosine. Two reactions transform tyrosine into DA: the first is catalysed by the enzyme tyrosine hydroxylase (TH) which converts tyrosine into l-3,4-dihydroxyphenylalanine (lDOPA). TH is considered the rate-limiting enzyme in this pathway. The second step is the decarboxylation of DOPA, catalysed by the enzyme aromatic l-amino acid decarboxylase (AADC), which produces DA. DA constitutes about 80% of the catecholamine content in the brain. Projections originating from brain areas that synthesize this neurotransmitter give rise to four axonal pathways: i) nigro-striatal, ii) mesolimbic, iii) mesocortical, iiii) tuberoinfundibular. The mesocortical pathway arises from the ventral tegmental area (VTA) and innervates different regions of the frontal cortex. This pathway seems involved in some aspects of learning and memory. The mesolimbic pathway originates from the midbrain VTA and innervates the ventral striatum (nucleus accumbens), the olfactory tubercle (OT) and parts of the limbic system. It has been implicated in influencing motivated behaviour. The tuberoinfundibular pathway arises from cells of the periventricular and arcuate nuclei of the hypothalamus. Projections of this pathway reach the median eminence of the hypothalamus where they release DA into the perivascular spaces of the capillary plexus of the hypothalamic–hypophyseal portal system. Thus, DA is transported to the anterior pituitary where it acts on the lactotrophs to inhibit the release of prolactin.

Projections constituting the nigrostriatal pathway arise from dopamine-synthesizing neurons of the midbrain nucleus, the substantia nigra compacta (SNc) which innervates the dorsal striatum (caudate-putamen). The nigrostriatal pathway is involved in the control of movement and its degeneration causes Parkinson’s disease, characterized by tremors, rigidity and akinesia, and resulting in hypodopaminergic activity of the central nervous system (CNS). On contrary, in schizophrenia, a hyperdopaminergic activity has been emphasized. Moreover, considerable evidences have also been accumulated, suggesting that both of these neurological disorders involving CNS dopaminergic system are associated with significant alterations in immune response.