Dopamine uptake during fast-phase endogenous dopamine release from mouse striatal synaptosomes

doi:10.1016/0304-3940(86)90265-X

Neuroscience Letters

Volume 71, Issue 1, 30 October 1986, Pages 106-112

https://doi.org/10.1016/0304-3940(86)90265-X Get rights and content

Abstract

[³H]Dopamine (DA) uptake and endogenous DA release were measured in mouse striatal P₂ synaptosomes over a 1–30-s period in the presence and absence of KCl depolarization. Approximately 70% of the total DA release over the 30-s period occurred within the first 5-s of depolarization. [³H]DA uptake over this same period was less than 5% of the corresponding release value. The magnitudes and rates of uptake were moderately inhibited by 30 mM KCl depolarization. These decreases were not fully explained by the reduction in sodium present during depolarization or by the dilution of labelled DA by released endogenous DA. Non-linear regression analysis of the uptake data revealed fast (< 1 s) and slow (> 1 s) components of uptake which were differentially affected by KCl depolarization. The results of this study indicate the presence of a rapid, multi-component synaptosomal DA uptake process which appears to play a small role in regulating in vitro endogenous DA release during the initial seconds of KCl depolarization. If synaptosomal uptake reflects the in vivo situation, presynaptic neuronal uptake may be more important in the long-term regulation of transmitter release by maintaining intracellular dopamine storage pools which are linked to synthesis and release processes.

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The evolution of dystonia-like movements in TOR1A rats after transient nerve injury is accompanied by dopaminergic dysregulation and abnormal oscillatory activity of a central motor network
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Citation Excerpt :
In our previously analyzed Tor1a+/− mouse model, administration of levodopa worsened DLM while treatment with a DA synthesis blocker reduced DLM, suggesting that a striatal overavailability of DA could trigger abnormal downstream signaling (Ip et al., 2016), similar to the dopaminergic mechanisms causing levodopa-induced dyskinesia in Parkinson's disease (Cenci and Crossman, 2018). Membrane depolarization induced by local potassium infusion is known to increase DA efflux; previous studies have revealed a reduction in striatal DA uptake in depolarized conditions due to internalization of DAT as a possible mechanism (Richardson et al., 2016; Woodward et al., 1986). It's known that torsinA influences DAT expression on the cell surface, which would in turn affect DA uptake and extracellular DA homeostasis (Torres et al., 2004).
TOR1A is the most common inherited form of dystonia with still unclear pathophysiology and reduced penetrance of 30–40%. ∆ETorA rats mimic the TOR1A disease by expression of the human TOR1A mutation without presenting a dystonic phenotype. We aimed to induce dystonia-like symptoms in male ∆ETorA rats by peripheral nerve injury and to identify central mechanism of dystonia development. Dystonia-like movements (DLM) were assessed using the tail suspension test and implementing a pipeline of deep learning applications. Neuron numbers of striatal parvalbumin⁺, nNOS⁺, calretinin⁺, ChAT⁺ interneurons and Nissl⁺ cells were estimated by unbiased stereology. Striatal dopaminergic metabolism was analyzed via in vivo microdialysis, qPCR and western blot. Local field potentials (LFP) were recorded from the central motor network. Deep brain stimulation (DBS) of the entopeduncular nucleus (EP) was performed. Nerve-injured ∆ETorA rats developed long-lasting DLM over 12 weeks. No changes in striatal structure were observed. Dystonic-like ∆ETorA rats presented a higher striatal dopaminergic turnover and stimulus-induced elevation of dopamine efflux compared to the control groups. Higher LFP theta power in the EP of dystonic-like ∆ETorA compared to wt rats was recorded. Chronic EP-DBS over 3 weeks led to improvement of DLM. Our data emphasizes the role of environmental factors in TOR1A symptomatogenesis. LFP analyses indicate that the pathologically enhanced theta power is a physiomarker of DLM. This TOR1A model replicates key features of the human TOR1A pathology on multiple biological levels and is therefore suited for further analysis of dystonia pathomechanism.
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Behavioral studies have indicated that the reinforcing effects of cocaine are dependent on inhibition of dopamine uptake in nucleus accumbens and prefrontal cortex. As it has been suggested that dopamine uptake and cocaine-inhibition of dopamine uptake may differ in nucleus accumbens, prefrontal cortex and striatum, we have further characterized dopamine uptake and its susceptibility to inhibition in these three regions. Dopamine uptake was resolved into two processes, which accounts for some of the apparent reported regional differences in sensitivity of dopamine to inhibition by cocaine. One, which is probably associated with uptake into dopaminergic terminals, was sensitive to 6-hydroxydopamine lesions, cocaine, GBR 12909 or ouabain and was dependent on temperature and sodium ion concentration; this was responsible for most of the observed uptake in tissue from striatum and nucleus accumbens, but not from prefrontal cortex. There appeared to be no regional difference in susceptibility of this mode of dopamine uptake to either cocaine or GBR 12909. The other type of dopamine uptake, which represented a significant proportion of the total in prefrontal cortex, but not in striatum or nucleus accumbens, was relatively insensitive to cocaine, GBR 12909 and ouabain and was dependent on temperature, but not sodium ion concentration. In addition, the cocaine-insensitive dopamine uptake was more sensitive to inhibition by dopamine than serotonin, but did not distinguish between dopamine and norepinephrine.
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Activity-dependent recruitment of endogenous glutamate for exocytosis
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The Ca²⁺-dependent release of the neurotransmitter glutamate from purified nerve terminals (synaptosomes) of the rat hippocampus was studied in a rapid perfusion apparatus. The response of the terminals was investigated with respect to the kinitics and duration of the release of endogenous glutamate upon brief and sustained stimulation and upon repetitive stimulation. The synaptosomes were stimulated by sustained chemical depolarization (0.5–3 min 30 mM K⁺). The cellular levels of glutamate, free Ca²⁺ and ATP in the nerve terminals were measured.
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It can be concluded that the capacity to release glutamate after brief depolarizations is fully restored during the repolarization period. However, if stimulation periods are of long duration (until termination of release), this capacity is no longer fully restored, especially with respect to a fast component of release. New glutamate is recruited only during the subsequent depolarization and with a delay. This points towards both activity- and time-dependent mechanisms. We hypothesize that different populations of synaptic vesicles are involved in the biphasic character of Ca²⁺-dependent glutamate release and in the activity- and time-dependent recruitment of glutamate: a “fusion ready” population released during a brief stimulation period and a “supplementary” population released during a sustained stimulation period.
Behavioral sensitization following a single apomorphine pretreatment - selective effects on the dopamine release process
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Once daily subchronic pretreatments with the dopamine (DA) agonist apomorphine (APO) increase striatal DA synthesis and metabolism. Such changes imply that adaptation to APO do not dissipate completely with in 24 h. In the present report we evaluated the effects of a single APO treatment 24 h prior to euthanasia on behavior and on striatal DA synthesis, metabolism, release and receptor binding. The single APO pretreatment reduced DA release from striatal synaptosomes. In contrast, striatal DA synthesis, metabolism, and the high-affinity binding of DA to the D₂ receptor were unaltered 24 h after agonist pretreatment. At this time the stereotypic response to a subsequent APO challenge was enhanced. This adaptive pattern is different from that observed 60 min following an acute APO pretreatment, when high-affinity D₂ binding is reduced. The pattern 24 h following a single APO pretreatment is also different from that observed following subchronic agonist dosing, when stereotypic behavior is enhanced, while basal DA synthesis and metabolism are increased.

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Dopamine uptake during fast-phase endogenous dopamine release from mouse striatal synaptosomes

Abstract

J. Neurosci. Meth.

Brain Res.

Life Sci.

Neurosci. Lett.

Catecholamine uptake by synaptosomes in homogenates of rat brain: stereospecificity in different areas

J. Pharmacol. Exp. Ther.

Initial release of 3H-dopamine from rat striatal synaptosomes: correlation with calcium entry

J. Neurosci.

The effects of various salts, temperature, and the alkaloids veratridine and batrachotoxin on the uptake of 3H-dopamine into synaptosomes from rat striatum

Mol. Pharmacol.

Initial release of ³H-dopamine from rat striatal synaptosomes: correlation with calcium entry

The effects of various salts, temperature, and the alkaloids veratridine and batrachotoxin on the uptake of ³H-dopamine into synaptosomes from rat striatum