Dopamine cells

Grace AA, Bunney BS, Moore H, Todd CL (1997) Dopamine-cell depolarization block as a model for the therapeutic actions of antipsychotic drugs. TINS 20 31-37... 

Ellinwood, E.H., Jr., and Lee, T. Effect of continuous systemic infusion of d-amphetamine on the sensitivity of nigral dopamine cells to apomorphine inhibition of firing rates. Brain Res 273 379-383, 1983. 

Figure 3. Sketch of DDC-expressing neurons in the Drosophila larval CNS. The CNS consists of brain lobes and a segmented ventral ganglion. Filled circles represent dopamine cells open circles represent serotonin cells grayed circles represent DDC cells that contain no detectable tyrosine hydroxylase or serotonin immunoreactivity, indicating that these cells may produce neither transmitter (Lundell and Hirsh, 1994). M, medial dopamine neurons VL, ventrolateral serotonin neurons DL, dorsolateral dopamine neurons. The hatched rectangle shows the region of the ventral ganglion that is shown in Figures 4 and 6.

Figure 4. DDC (A), serotonin (B), and tyrosine hydroxylase (C) immunore-activity in the posterior region of a wild-type Drosophila ventral ganglion. Tyrosine hydroxylase (TH) encodes the rate-limiting step in dopamine biosynthesis and is a marker for dopamine cells. B and C are the same CNS assayed for both serotonin and TH. M, medial dopamine neurons VL, ventrolateral serotonin neurons DL, dorsolateral dopamine neurons. Short unmarked arrows in C show vacuolated cells that do not contain DDC immunoreactivity. The immunoreactivity in these cells may represent a nonspecific cross-reactivity of the rat TH antibody. The length bar in A is 50 pM. The images are confocal projections generated on a Molecular Dynamics-2000 confocal laser scanning microscope.

The majority of DDC-expressing cells in the brain lobes are dopamine cells. Most of these dopamine cells have axons that project into a common axonal fiber extending anteriomedially within the brain lobe and then separating into finer fibers that cross between the lobes. The dopamine cells occur in small clusters of two to six cells, which suggests that these cells might share common lineages. The serotonin cells within the lobes are also found in pairs, and each pair projects axons into closely associated tracts. The pathways of the serotonin tracts often parallel those of the dopamine cells but are distinct (Lundell and Hirsh, 1994). 

Figure 4 shows confocal images of the staining pattern for DDC (Fig. 4A), serotonin (Fig. 4B), and TH (Fig. 4C) in the segmental ventral ganglion of the CNS from third instar larvae. Panels B and C are the same CNS double stained with serotonin and TH. The DDC-expressing cells can be categorized into a set of paired ventral lateral serotonin cells (Fig. 4A,B labeled VL in 4A), and two morphologically distinct types of dopamine cells, the medial dopamine cells (Fig. 4A,C labeled M) and the dorsal-lateral dopamine cells (Fig. 4A,C labeled DL). Figure 4 demonstrates clearly that individual DDC cells synthesize either serotonin or dopamine, but not both. One additional set of cells shows TH immunoreactivity in the ventral ganglion. These six large vacuolated cells are located more laterally than any other DDC cells (Fig. 4C, unlabeled short arrows). It is likely that the immunoreactivity in these cells results from a non-specific cross-reaction, since these cells are not...

The axonal projections from the DDC-expressing cells in the ventral ganglion also show tendencies to follow common pathways. The projections from the ventral lateral serotonin cells extend medially to fuse with axons projecting from the contralateral serotonin cells. At the midline, this projection is met by an axonal projection from the medial dopamine cell. 

Figure 8. Colocalization of DDC and ZFH-2 in larval CNS. This figure shows abdominal segments 4-7 of a third instar larval CNS. DDC im-munoreactivity is cytoplasmic and is shown in red, whereas ZFH-2 im-munoreactivity is nuclear and is shown in green. Only the outside cell of each pair of serotonin neurons expresses ZFH-2. One medial dopamine cell shown at the top also shows ZFH-2 expression. This projection does not include the dorsolateral cells, which also express ZFH-2. A similar projection has been published in Lundell and Hirsh (1992).

Bjorklund A., Skagerberg G. (1979). Evidence for a major spinal cord projection from the diencephalic All dopamine cell group in the rat using transmitter-specific fluorescent retrograde tracing. Brain Res. 177(1), 170-5. 

Sesack, S. R. and Carr, D. B. Selective prefrontal cortex inputs to dopamine cells implications for schizophrenia. Physiol. Behav. 77 513-517,2002. 

Rimcazole (BW 234U) (496) is a novel anti-pyretic, neuroleptic agent. It was found to be a specific competitive antagonist of a-sites in the brain. It reverses psychotic conditions induced in humans by phencyclidine and/or a-opiod antagonists, probably by binding to receptors in the brain (459-461). Rimcazole has an indirect effect on dopamine neurons with relative selectivity for AlO dopamine cells (462). 

Diana, M. (1998) Drugs of abuse and dopamine cell activity. Adv Pharmacol 42 998-1001. 

Grenhoff, J. and Svensson, T.H. (1989) Clonidine modulates dopamine cell firing in rat ventral tegmental area. Eur J Pharmacol 165 11-18. 

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). 

Dopamine Cell bodies at all levels short, medium, and long connections Di Phenothiazines Inhibitory ( ) t cAMP... 

The other question that the imputation of an active role for dopamine in dreams raises is, where is the dopamine coming from Although there are dopamine cells that innervate local circuits in such forebrain sites as the hypothalamus, all of the dopamine cells which project to the rest of the brain are in the brain stem What becomes of Solms s theory of the independence of forebrain dream instigators if much or most of the dopamine released there is related to cellular activity in the midbrain ... 

FIGURE 11—17. Serotonin-dopamine interactions in the nigrostriatal dopamine pathway. Serotonin inhibits dopamine release, both at the level of dopamine cell bodies in the brainstem substantia nigra and at the level of the axon terminals in the basal ganglia—neostriatum (see also Figs. 11 — 18 through 11 —20). In both cases, the release of serotonin acts as a brake on dopamine release. 

In addition to MPTP, other endogenously produced neurotoxins, namely, the monoamine-derived 1,2,3,4-tetrahydroisoquinolines and 6,7-dihydroxy-l,2,3,4-tetrahydroisoquinolines, have been proposed as factors accelerating dopamine cell death. A-methylated isoquinolines were found to be oxidized by MAO, and hydroxyl radicals were found to be produced by this reaction. In addition, by incubation with the A-methylated isoquinolines, ATP was depleted from a dopaminergic cell model. Pretreatment of the cells with MAO inhibitors such as selegiline could, however, protect against ATP depletion. These results suggest that oxidation of neurotoxic isoquinolines is directly involved in the oxidative stress to induce the cell death of dopamine neurons. On the other hand, 1 -methyl-1,2,3,4-tetrahydroisoquinoline and 1 -methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquino-... 

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