Central substantia nigra

The nigrostriatal tract is one of the four main dopaminergic pathways in the central nervous system. About 75% of the dopamine in the brain occurs in the nigrostriatal pathway with its cell bodies in the substantia nigra, whose axons project in the corpus striatum. Degeneration of the dopaminergic neurons in the nigrostriatal system results in Parkinsons disease. 

Benkirane, S. Arbilla, S. and hanger, S.Z. A functional response to D1 dopamine receptor stimulation in the central nervous system Inhibition of the release of [ H]-serotonin from the rat substantia nigra. Naunyn-Schmiedebergs Arch Pharmacol 335 502-507, 1987. 

Figure 7.4 Summary of some of the wide array of afferent and efferent connections of midbrain dopaminergic neurons (SN/A9, RRF/A8, and VTA/A10 in center of figure). This emphasizes their potential involvement in coordination of seemingly disparate behaviors inclusive of the sleep-wake state of the organism. Abbreviations BP, blood pressure BST, bed nucleus of the stria terminalis CEA, central nucleus of the amygdala MEA, midbrain extrapyramidal area NTS, nucleus of the solitary tract O2, oxygen tension PPN, pedunculopontine tegmental nucleus RRF, retrorubral field SN, substantia nigra VTA, ventral tegmental area.

Mesencephalon substantia nigra-pars reticulata, interpeduncular nucleus, central gray ventral tegmental area, laterodorsal tegmental nucleus, interpeduncular nucleus... 

The new work has established that a neurodegenerative pathway leading from soluble to insoluble, filamentous a-synuclein is central to Lewy body diseases and multiple system atrophy. The development of experimental models of a-synucleinopathies has opened the way to the identification of the detailed mechanisms by which the formation of inclusions causes disease. These model systems have also made it possible to identify disease modifiers that may well lead to the development of the first mechanism-based therapies for these diseases. At a conceptual level, it will be important to understand whether a-synuclein has a role to play in disorders, such as autosomal-recessive juvenile forms of parkinsonism caused by mutations in the Parkin, DJ-1 and PINK-1 genes, or whether there are entirely separate mechanisms by which the dopaminergic nerve cells of the substantia nigra degenerate in Parkinson s disease and in inherited disorders with parkinsonism. 

Firing rate of substantia nigra DA neurons increased Recovery from depressed firing rate of VTA DA neurons D 1-like antagonist in amygdala doesn t precipitate withdrawal Reduced amygdala central nucleus DA... 

The mechanism of the neurological symptoms in Parkinson s disease was discovered from the ability of reserpine to cause akinesia in humans by the depletion of central catecholamine stores. The dopamine levels in patients who died from parkinsonism were found to be extremely low because of deterioration of the dopaminergic neuronal cell bodies and the pathways connecting the substantia nigra with the corpus striatum. 

SSRIs reduce dopamine cell firing in the substantia nigra through their effects on serotonin input to this nucleus. The net result is that they can cause generally mild extrapyramidal side effects (EPS) (500). The most common are restlessness and tremors. The same mechanism is probably responsible for their interaction with other agents that affect central motor systems. Thus, the SSRIs can potentiate the tremor seen with lithium, as well as EPS caused by antipsychotics, bupropion, and psychostimulants (376, 500). 

As indicated in Table I, I-III and their R and S optical antipodes were studied for dopaminergic activity in four primary tests (1) stimulation of central DA-sensitive adenylate cyclase (2, 35), (2) displacement of [%]-spiroperidol binding to rat caudate homogenate (35, 40), (3) induction of rotations in rats with unilateral lesions of the left substantia nigra (2, ... 

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