The dopamine transporter and dopamine D2 receptor messenger RNAs are differentially expressed in limbic- and motor-related subpopulations of human mesencephalic neurons

Hurd, Yasmin L.; Pristupa, Zdenek B.; Herman, M M; Niznik, H. B.; Kleinman, Joel E.

doi:10.1016/0306-4522(94)90535-5

Cited by 80 publications

(46 citation statements)

References 28 publications

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“…On the other hand, the heterogeneity in D 2 receptor control is strongly consistent with accumulating evidence of greater expression levels of D 2 protein in SNc than in VTA (Bouthenet et al, 1987;Morelli et al, 1988;Sales et al, 1989;Mansour et al, 1990;Le Moine and Bloch, 1991;Hurd et al, 1994). In particular, stronger autoinhibition of release in SNc than in VTA may be attributable to differential D 2 receptor expression levels in the two tiers of neurons that comprise the midbrain DA cell groups.…”

Section: Receptor Modulation Of Somatodendritic Da Release In Sncsupporting

confidence: 53%

“…Ventral tier neurons found only in ventral SNc (Fallon and Moore, 1978;Gerfen et al, 1985Gerfen et al, , 1987 have higher expression and protein levels of the D 2 receptor than dorsal tier cells found in dorsal SNc and throughout VTA (Chiodo et al, 1984;Shimada et al, 1992;Blanchard et al, 1994;Hurd et al, 1994;Sanghera et al, 1994;Ciliax et al, 1995;Freed et al, 1995). Similarly, the greater activity of DA uptake process via the DAT in SNc than in VTA might be attributable to the greater expression levels of the DAT in ventral tier cells (Shimada et al, 1992;Blanchard et al, 1994;Hurd et al, 1994;Sanghera et al, 1994;Ciliax et al, 1995;Freed et al, 1995). In any event, reduced autoreceptor control and uptake via the DAT in VTA suggest that released DA may be under a less strict regulation in VTA than in the adjacent SNc.…”

Section: Receptor Modulation Of Somatodendritic Da Release In Sncmentioning

confidence: 99%

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Differential Autoreceptor Control of Somatodendritic and Axon Terminal Dopamine Release in Substantia Nigra, Ventral Tegmental Area, and Striatum

1997

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Dopamine (DA) is released from somatodendritic sites of neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA), where it has neuromodulatory effects. The aim of this study was to evaluate the role of D 2 autoreceptor inhibition in the regulation of this somatodendritic release in each region. Fast cyclic voltammetry at carbon fiber microelectrodes was used to measure electrically evoked DA release in vitro. Furthermore, we compared D 2 regulation of somatodendritic release with the more familiar axon terminal release in caudate putamen (CPu) and nucleus accumbens (NAc). Evoked DA release was TTX-sensitive at all sites. There was significant D 2 autoinhibition of DA release in SNc; however, this mechanism was two-to threefold less powerful, as compared with axon terminal release in CPu. In contrast to SNc, somatodendritic release in VTA was not under significant D 2 receptor control, whereas release in the respective axon terminal region (NAc) was controlled strongly by autoinhibition. Thus, these data indicate that, first, autoinhibition via D 2 receptors consistently plays a less significant role in the control of somatodendritic than axon terminal DA release, and, second, even at the level of somatodendrites themselves, D 2 autoinhibition displays marked regional variation. In the light of previous data indicating that DA uptake processes are also less active in somatodendritic than in terminal regions, these results are interpreted as indicating that DA transmission is regulated differently in somatodendritic zones, as compared with axon terminals, and thus may have different functional consequences.

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Section: Receptor Modulation Of Somatodendritic Da Release In Sncsupporting

confidence: 53%

Section: Receptor Modulation Of Somatodendritic Da Release In Sncmentioning

confidence: 99%

Differential Autoreceptor Control of Somatodendritic and Axon Terminal Dopamine Release in Substantia Nigra, Ventral Tegmental Area, and Striatum

1997

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“…However, in the present study we found both D 2 receptor sites and mRNA in all dopaminergic cell groups of the midbrain, including the VTA. Hurd et al (1994) have also observed D 2 receptor mRNA in the VTA, but at levels significantly lower than the SN. The reason for this discrepancy between the results of Meador-Woodruff and associates (1994a) and our work is unclear.…”

Section: Discussionmentioning

confidence: 71%

Distribution of Dopamine D3 Receptor Expressing Neurons in the Human Forebrain Comparison with D2 Receptor Expressing Neurons

Gurevich

Joyce

1999

Neuropsychopharmacology

409

294

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“…In contrast, the DAT gold particles that are present in dopaminergic somata are selectively located on intracellular membranes. Thus, although there may be quantitative differences in the expression of DAT in the SN and VTA (Blanchard et al, 1994;Hurd et al, 1994;Haber et al, 1995;Cragg et al, 1997), we did not detect any qualitative differences in the subcellular targeting of DAT to plasma membranes in the two regions. We did, however, observe important differences in the cellular relationships between DAT-labeled neurons in the VTA and SN.…”

Section: Comparison With the Substantia Nigra (Sn)mentioning

confidence: 63%

Immunogold Localization of the Dopamine Transporter: An Ultrastructural Study of the Rat Ventral Tegmental Area

et al. 1997

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The dopamine transporter (DAT) plays an important role in the plasmalemmal reuptake of dopamine and, thus, in the termination of normal dopaminergic neurotransmission. DAT is also a major binding site for cocaine and other stimulants, the psychoactive effects of which are associated primarily with the inhibition of dopamine reuptake within mesocorticolimbic dopaminergic neurons. We used electron microscopy with an anti-peptide antiserum directed against the N-terminal domain of DAT to determine the subcellular localization of this transporter in the rat ventral tegmental area (VTA), the region that contains the cell bodies and dendrites of these dopaminergic neurons. We show that in the VTA, almost 95% of the DAT immunogold-labeled profiles are neuronal perikarya and dendrites, and the remainder are unmyelinated axons. Within perikarya and large proximal dendrites, almost all of the DAT immunogold particles are associated with intracellular membranes, including saccules of Golgi and cytoplasmic tubulovesicles. In contrast, within medium-to smalldiameter dendrites and unmyelinated axons, most of the DAT gold particles are located on plasma membranes. In dually labeled tissue, peroxidase reaction product for the catecholaminesynthesizing enzyme tyrosine hydroxylase is present in DATimmunoreactive profiles. These findings suggest that intermediate and distal dendrites are both the primary sites of dopamine reuptake and the principal targets of cocaine and related psychostimulants within dopaminergic neurons in the VTA.

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The dopamine transporter and dopamine D2 receptor messenger RNAs are differentially expressed in limbic- and motor-related subpopulations of human mesencephalic neurons

Cited by 80 publications

References 28 publications

Differential Autoreceptor Control of Somatodendritic and Axon Terminal Dopamine Release in Substantia Nigra, Ventral Tegmental Area, and Striatum

Differential Autoreceptor Control of Somatodendritic and Axon Terminal Dopamine Release in Substantia Nigra, Ventral Tegmental Area, and Striatum

Distribution of Dopamine D3 Receptor Expressing Neurons in the Human Forebrain Comparison with D2 Receptor Expressing Neurons

Immunogold Localization of the Dopamine Transporter: An Ultrastructural Study of the Rat Ventral Tegmental Area

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