Dopaminergic pathways

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. 

The nucleus accumbens is part of the limbic system. It receives dopaminergic input through the mesolimbic system that originates from cell bodies in the ventral segmental area (A 10 cell group). This mesolimbic dopaminergic pathway is part of the reward pathways. Drugs of abuse (cocaine, amphetamine, opiates or nicotine) have been shown to increase the level of dopamine release in these neurons. 

It could not be anticipated that the extension of the alpha-methyl of MDMA to an alpha-ethyl would also attenuate the effects of the compound on dopaminergic pathways in the brain. In contrast to MDMA, MBDB has no significant effect either on inhibition of uptake of dopamine into striatal synaptosomes (Steele et al. 1987) or on release of dopamine from caudate... 

Nemeroff C. The interaetion of neurotensin with dopaminergic pathways in the central nervous system Basie neurobiology and implications for the pathogenesis and treatment of schiiphrenia. Psychoneuroendocrinology ll(l) 15-37, 1986. 

Hokfelt T., Phillipson 0., Goldstein M. (1979). Evidence for a dopaminergic pathway in the rat descending from the All cell group to the spinal cord. Acta Physiol Scand. 107(4), 393-5. 

Spanagel R., Herz A., Shippenberg T. Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. Proc. Natl. Acad. Sci. U.S.A. 89 2046, 1992. 

Drugs stimulate receptors on the cell bodies of dopaminergic neurons causing dopamine release and stimulating postsynaptic dopamine receptors in the nucleus accumbens, supposedly resulting in the perception of pleasure [1]. Other hypotheses suggest that these mesolimbic dopaminergic pathways are necessary for the... 

Muscarinic and dopaminergic pathways in the CNS interact in control of numerous pathways implicated in diseases, especially those controlling involuntary motor systems. Muscarinic effects on dopamine release are mediated in several ways via different mAChR subtypes. Thus mAChR facilitation of DA release appears to involve M4 receptors on GABA projection neurons to the striatum, while M3 receptors on striatal DA neurons are predicted to inhibit striatal DA release [12],... 

A recent study further supported the involvement of dopamine in the mechanism of antidepressants [82]. In this study, the antidepressant-like effect of citalo-pram, paroxetine, desipramine and imipramine in the mouse forced swim test (FST) was compared with and without dopamine depletion. It was found that lesioning with 6-OHDA did not affect the response of mice to desipramine and imipramine, whereas dopamine depletion abolished the antidepressant-like effect of citalopram and paroxetine. These results suggest that the antidepressant-like effect of SSRIs in the FST requires the activation of dopaminergic pathways. 

Important functional interactions of the dopaminergic and other key neurochemical systems have also been demonstrated. Durkin et al., (1986) reported that dopamine in the septum inhibits acetylcholine release in the hippocampus, whilst destruction of the A-10 septal dopaminergic pathways in mice results in increased choline acetyltransferase (Yanai et al., 1993). Pharmacological reduction of nigral dopamine levels to 5% of normal in guinea pigs results in a marked increase (over 70%) in the spontaneous release of acetyl-... 

Frisch, A., Michaelovsky, E., Rockah, R., Amir, L, Hermesh, H., Laor, N., Fuchs, C., Zohar, J., Lerer, B., Buniak, S.E, Landa, S., Poyurovsky, M., Shapira, B., and Weizman, R. (2000) Association between obsessive-compulsive disorder and polymorphisms of genes encoding components of the serotonergic and dopaminergic pathways. Eur Neuropsychopharmacol 10 205-209. 

---