3,4‐Dihydroxyphenylacetic acid and 4‐hydroxy‐3‐methoxyphenylacetic acid in the mouse striatum: a reflection of intra‐ and extra‐neuronal metabolism of dopamine?

Roffler-Tarlov, Suzanne; Sharman, D. F.; P, Tegerdine

doi:10.1111/j.1476-5381.1971.tb07118.x

Cited by 180 publications

(46 citation statements)

References 12 publications

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“…40 DOPAC is formed primarily within the presynaptic neuron and is therefore a measure of intraneuronal turnover. 41 The chemical profile suggests higher DA release and tone in the striatum (higher 3-MT and DA concentration), but greater …”

Section: ■ Results and Discussionmentioning

confidence: 99%

Chemical Gradients within Brain Extracellular Space Measured using Low Flow Push–Pull Perfusion Sampling in Vivo

Slaney

Mabrouk

Porter-Stransky

et al. 2012

ACS Chem. Neurosci.

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Although populations of neurons are known to vary on the micrometer scale, little is known about whether basal concentrations of neurotransmitters also vary on this scale. We used low-flow push−pull perfusion to test if such chemical gradients exist between several small brain nuclei. A miniaturized polyimide-encased push−pull probe was developed and used to measure basal neurotransmitter spatial gradients within brain of live animals with 0.004 mm 3 resolution. We simultaneously measured dopamine (DA), norepinephrine, serotonin (5-HT), glutamate, γ-aminobutyric acid (GABA), aspartate (Asp), glycine (Gly), acetylcholine (ACh), and several neurotransmitter metabolites. Significant differences in basal concentrations between midbrain regions as little as 200 μm apart were observed. For example, dopamine in the ventral tegmental area (VTA) was 4.8 ± 1.5 nM but in the red nucleus was 0.5 ± 0.2 nM. Regions of high glutamate concentration and variability were found within the VTA of some individuals, suggesting hot spots of glutamatergic activity. Measurements were also made within the nucleus accumbens core and shell. Differences were not observed in dopamine and 5-HT in the core and shell; but their metabolites homovanillic acid (460 ± 60 nM and 130 ± 60 nM respectively) and 5-hydroxyindoleacetic acid (720 ± 200 nM and 220 ± 50 nM respectively) did differ significantly, suggesting differences in dopamine and 5-HT activity in these brain regions. Maintenance of these gradients depends upon a variety of mechanisms. Such gradients likely underlie highly localized effects of drugs and control of behavior that have been found using other techniques.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Chemical Gradients within Brain Extracellular Space Measured using Low Flow Push–Pull Perfusion Sampling in Vivo

Slaney

Mabrouk

Porter-Stransky

et al. 2012

ACS Chem. Neurosci.

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“…However, by the 22-h time point, the DA metabolite, DOPAC, had recovered to predrug levels. This observation suggests that the releasable pool of transmitter had been replenished, since DOPAC originates primarily from the metabolism of cytoplasmic DA (Roffler-Tarlov et al, 1971;Westerink and Korf, 1976). Alternatively, it is possible that DAT internalization, once promoted by the initial high extracellular transmitter concentrations, persisted throughout the drug response even after METH levels significantly declined.…”

Section: Neurochemical Profilementioning

confidence: 93%

Human Methamphetamine Pharmacokinetics Simulated in the Rat: Single Daily Intravenous Administration Reveals Elements of Sensitization and Tolerance

Segal

Kuczenski

2005

Neuropsychopharmacol

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We developed a computer-controlled intravenous methamphetamine (METH) administration procedure (dynamic infusion), which enables us to compensate for an important pharmacokinetic difference between rats and humans by imposing a 12-h half-life for the drug in rats. Dynamic infusion of 0.5 mg/kg METH produced a pharmacokinetic profile that closely simulates the METH exposure pattern in humans, including an apparent half-life of 11.671.3 h, and an area under the concentration vs time curve of 9.4 mM h, about 20-fold larger than results obtained with typical rat pharmacokinetics. Using this procedure, METH produced a prolonged behavioral stimulation and elevation in caudate extracellular dopamine (DA). Both the behavioral and the DA effects exhibited tolerance to the sustained plasma METH exposure. Single daily dynamic infusion of 0.5 mg/kg METH for 15 days resulted in a progressive enhancement of the behavioral response until about Day 10. On subsequent days, in addition to continued evidence of sensitization, tolerance in the form of a marked decrease in the duration of the behavioral activation became a prominent feature of the response. Qualitative changes in the behavior also emerged. Resumption of METH treatment following 4 days of withdrawal revealed that sensitization was apparent during the first dynamic infusion, and that tolerance re-emerged within two additional days of drug administration. These results showed that a humanlike METH exposure pattern produced behavioral and striatal DA response profiles that are both quantitatively and qualitatively different from the effects typically observed with single daily METH injections in rats. Thus, simulation of human METH exposure patterns may be a critical prerequisite to identifying mechanisms relevant to the chronic use of this drug in humans. Neuropsychopharmacology (2006) 31, 941-955.

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“…Thus the total amount of DA formed during this time would be larger than that indicated by the observed increase in the concentration of DA. It has been shown that in the mouse brain DOPAC is not normally metabolized to HVA to any great extent (Murphy et al, 1969;Roffler-Tarlov, Sharman & Tegerdine, 1971), and the latter authors have suggested that the DOPAC in the striatum is formed within the DA-containing neurones. However, the posibility that y-hydroxybutyrate prevents the efflux of DOPAC as well as DA from the nerves must not be ignored.…”

Section: Discusionmentioning

confidence: 99%

The effect of sodium γ‐hydroxybutyrate on the metabolism of dopamine in the brain

Hutchins

Rayevsky

Sharman

1972

British J Pharmacology

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Summary1. Sodium gamma hydroxybutyrate (GHB-Na), when given to rats and mice, caused a sleep-like state and a fall in body temperature of about 10°C. 2. GHB-Na produced a dose-dependent increase in the concentration of dopamine (DA) in the brains of mice kept at an environmental temperature of 1820o C or 30-32o C. 3. The concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) and 4-hydroxy-3-methoxyphenylacetic acid (HVA), the metabolites of DA, were increased in the striatal tissues of rats and mice, after the administration of GHB-Na. However there was a delay of 60 mi before the concentration of HVA increased whereas there appeared to be little delay before the concentration of DOPAC increased.4. When GHB-Na was administered to reserpine-treated animals, no increase occurred in the concentration of dopamine in the brains of mice or rats, or of DOPAC in the rat brain. 5. Reserpine did not prevent the induction of the sleep-like state by GHB-Na. 6. The results presented suggest that the effect of GHB-Na in increasing the concentration of DA requires unimpaired storage mechanisms for the amine.

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3,4‐Dihydroxyphenylacetic acid and 4‐hydroxy‐3‐methoxyphenylacetic acid in the mouse striatum: a reflection of intra‐ and extra‐neuronal metabolism of dopamine?

Cited by 180 publications

References 12 publications

Chemical Gradients within Brain Extracellular Space Measured using Low Flow Push–Pull Perfusion Sampling in Vivo

Chemical Gradients within Brain Extracellular Space Measured using Low Flow Push–Pull Perfusion Sampling in Vivo

Human Methamphetamine Pharmacokinetics Simulated in the Rat: Single Daily Intravenous Administration Reveals Elements of Sensitization and Tolerance

The effect of sodium γ‐hydroxybutyrate on the metabolism of dopamine in the brain

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