Neurochemical Studies of the Mesolimbic Dopaminergic Pathway: Somatodendritic Mechanisms and GABAergic Neurones in the Rat Ventral Tegmentum

Beart, Philip M; McDonald, D.

doi:10.1111/j.1471-4159.1980.tb11253.x

Cited by 55 publications

(28 citation statements)

References 42 publications

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“…3H-DA uptake was measured after incubation of the cells with 3H-DA, 10 • 10 -gM, in the presence of pargyline, 10 5 M, and ascorbic acid, 10 -3M, at 37~ for 30 rain. Non-specific uptake/ binding was calculated at 0~ and/or in the presence of 10 -SM mazindol (Beart and McDonald, 1980). Proteins were measured according to Bradford (1976).…”

Section: Studies In Fetal Mid Brain Rat Neuronsmentioning

confidence: 99%

Fibroblast growth factors: Structure-activity on dopamine neurons in vitro

Mena¹,

Casarejos²,

Giménez‐Gallego

et al. 1995

J Neural Transm Gen Sect

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We investigated the effect of neurotrophic factors on dopamine (DA) cells in vitro. At concentrations of nanograms/c.c. basic fibroblast growth factor (bFGF) is a more potent DA-trophic agent than brain derived neurotrophic factor (BDNF) or epidermal growth factor (EGF) in fetal mid brain neurons. In these cells, bFGF produces a greater increase of DA levels and percentage of cells positive for tyrosine hydroxylase (TH+) than BDNF and EGF. Acidic fibroblast growth factor (aFGF) was not tested in fetal DA cells since aFGF requires heparin for its effect and fetal mid brain cultures do not grow well in the presence of a high concentration of heparin. We further investigated the effect of bFGF and aFGF, and two of their analogs, in catecholamine rich human neuroblastoma cells NB69. In these cells aFGF, at concentrations of picograms/c.c., increases DA levels, while its analogs, E118 and super short, have no effect. Acidic FGF also increases norepinephrine levels, the number of TH+ cells, and the percentage of TH+ with respect to the total number of nuclei. Basic fibroblast growth factor (bFGF) produced similar, but less potent effects. Acidic FGF was active only in the presence of heparin; the effect of bFGF was independent of heparin. FGFs are promising drugs for the treatment of PD, though further investigations with these compounds should be performed before their use in clinical trials.

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Section: Studies In Fetal Mid Brain Rat Neuronsmentioning

confidence: 99%

Fibroblast growth factors: Structure-activity on dopamine neurons in vitro

Mena¹,

Casarejos²,

Giménez‐Gallego

et al. 1995

J Neural Transm Gen Sect

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“…TH activity was measured according to the rate of accumulation of DOPA after inhibition of its decar-boxylation by NSD 1015, 100 mg/liter, for 30 min (Carlsson et al, 1972). High affinity 3H-DA uptake was evaluated according to Beart and McDonald (1980) and choline acetyltransferase (CAT) activity according to Galea and Estrada (1991).…”

Section: Studies With Neuroblastoma Cells Nb69mentioning

confidence: 99%

Effects of retinoic acid on NB 69 human neuroblastoma cells and fetal rat mid brain neurons

Mena¹,

Casarejos²,

Estrada

et al. 1994

J Neural Transm Gen Sect

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Retinoids are chemical compounds which play important roles in ontogenetic development and cranio-caudal differentiation in animals, but their effect on phenotypic expression of neurotransmitters are unknown. We studied the pharmacological and morphological effects of retinoic acid (RA) on two types of immature vertebrate neurons, the human derived neuroblastoma cells, NB69, and fetal rat mid brain neurons in culture. The pharmacological effects of RA on the cultures and their relation to catecholamine and acetylcholine neurotransmission were evaluated according the levels of catecholamines, tyrosine hydroxylase (TH) activity, TH immunostaining, and choline acetyltransferase (CAT) activity, respectively. RA reduces catecholamine levels and TH activity in NB69 cells and the number of dopamine neurons in cultures derived from rat fetal mid brain. The detrimental effect of RA on mid brain neurons is dose- dependent; limited to TH+ cells at low concentrations (100 to 500 nM) and toxic for all types of cells at high concentrations (1 to 2 microM). RA increases CAT activity in NB 69 cells and produces phenotypic differentiation of these to a more mature neuronal phenotype with more prolonged neurite extensions. Therefore, RA may play a trophic positive role in the differentiation of immature cells to cholinergic neurons; this contrasts with the detrimental effects of RA on catecholamine neurons.

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“…Accordingly, several lines of evidence have shown that there is functional expression of DAT in this region. Autoradiographic uptake experiments, for example, have demonstrated the presence of sodium-dependent dopamine uptake in the VTA that is sensitive to DAT inhibitors (Beart et al, 1979;Beart and McDonald, 1980). In addition, the local application of DAT-inhibiting drugs in the VTA has been shown to increase extracellular levels of dopamine (Kalivas and Duffy, 1991;Chen and Reith, 1994), leading to inhibition of dopaminergic cell firing in this region (Einhorn et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

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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Neurochemical Studies of the Mesolimbic Dopaminergic Pathway: Somatodendritic Mechanisms and GABAergic Neurones in the Rat Ventral Tegmentum

Cited by 55 publications

References 42 publications

Fibroblast growth factors: Structure-activity on dopamine neurons in vitro

Fibroblast growth factors: Structure-activity on dopamine neurons in vitro

Effects of retinoic acid on NB 69 human neuroblastoma cells and fetal rat mid brain neurons

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

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