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Cited by 48Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchParkinson's Disease Mechanisms and Treatments

Amphetamine augments vesicular dopamine release in the dorsal and ventral striatum through different mechanisms

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Avelar, Alicia J., Juliano, Steven A., Garris, Paul A.·2013·Journal of Neurochemistry
DOI 10.1111/jnc.12197PMC PMC3633730
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Abstract

Amphetamine has well‐established actions on pre‐synaptic dopamine signaling, such as inhibiting uptake and degradation, activating synthesis, depleting vesicular stores, and promoting dopamine‐transporter reversal and non‐exocytotic release. Recent in vivo studies have identified an additional mechanism: augmenting vesicular release. In this study, we investigated how amphetamine elicits this effect. Our hypothesis was that amphetamine enhances vesicular dopamine release in dorsal and ventral striata by differentially targeting dopamine synthesis and degradation. In urethane‐anesthetized rats, we employed voltammetry to monitor dopamine, electrical stimulation to deplete stores or assess vesicular release and uptake, and pharmacology to isolate degradation and synthesis. While amphetamine increased electrically evoked dopamine levels, inhibited uptake, and up‐regulated vesicular release in both striatal sub‐regions in controls, this psychostimulant elicited region‐specific effects on evoked levels and vesicular release but not uptake in drug treatments. Evoked levels better correlated with vesicular release compared with uptake, supporting enhanced vesicular release as an important amphetamine mechanism. Taken together, these results suggested that amphetamine enhances vesicular release in the dorsal striatum by activating dopamine synthesis and inhibiting dopamine degradation, but targeting an alternative mechanism in the ventral striatum. Region‐distinct activation of vesicular dopamine release highlights complex cellular actions of amphetamine and may have implications for its behavioral effects.

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  • The primary pharmacologic effect of both amphetamine and methylphenidate is to increase central dopamine and norepinephrine activity.

    “The primary pharmacologic effect of both amphetamine and methylphenidate is to increase central dopamine and norepinephrine activity, which impacts executive and attentional function.”

    From The pharmacology of amphetamine and methylphenidate: Relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities (2018) · cites this paper as [44]

    The Introduction describes amphetamine’s actions on dopamine signaling, and the Discussion section “DAT Inhibitors and Vesicular DA Release” identifies methylphenidate as a dopamine-transporter inhibitor that augments dopamine release (page numbers unavailable). These passages support a dopaminergic effect for both drugs, but do not establish that increasing both dopamine and norepinephrine activity is their primary pharmacologic effect. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Amphetamine increases synaptic extracellular dopamine and norepinephrine levels.

    “The main mechanism of action of AMP is to increase synaptic extracellular DA and NE levels (44, 52, 59, 60, 67, 68, 71, 78, 80, 85, 87, 94, 105, 107, 128).”

    From The pharmacology of amphetamine and methylphenidate: Relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities (2018) · cites this paper as [44]

    The Introduction (page unavailable) describes amphetamine’s effects on dopamine signaling, including dopamine release and inhibition of its uptake. The Discussion (page unavailable) also describes amphetamine-induced increases in extracellular dopamine signals. Neither passage supports the attributed increase in norepinephrine, which this paper does not examine. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Amphetamine's effect on synaptic dopamine and norepinephrine is mediated by inhibition of dopamine and norepinephrine transporters, reducing reuptake.

    “This effect is mediated by inhibition of DA transporters (DAT) and NE transporters (NET) (44, 52, 58), which reduces the reuptake of these molecules from the synapse.”

    From The pharmacology of amphetamine and methylphenidate: Relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities (2018) · cites this paper as [44]

    The Introduction says amphetamine inhibits the dopamine transporter, and the Discussion (“DAT Inhibitors and Vesicular DA Release”; page unavailable) reports that it inhibits dopamine uptake. The paper does not address norepinephrine-transporter inhibition or norepinephrine reuptake. It also identifies enhanced vesicular dopamine release as another important mechanism, so it does not support attributing the whole effect solely to reduced reuptake. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Authors
Avelar, A. J., Juliano, S. A., & Garris, P. A.
Affiliations
Illinois State University (US)
Corresponding author
Garris, Paul A.
ORCID
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2013-03-06
Volume
125
Issue
3
Pages
373-385
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
DOI
10.1111/jnc.12197
PMC
PMC3633730
OpenAlex
W1975084855
Cited by
48
References
0
Citations by year
2025: 3 · 2024: 3 · 2023: 5 · 2022: 3 · 2021: 5 · 2020: 1 · 2019: 7 · 2018: 3 · 2017: 1 · 2016: 3 · 2015: 5 · 2014: 6 · 2013: 3
FWCI
2.78
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute on Drug Abuse (R03DA021770, DA021770)
  • Division of Biological Infrastructure
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords
amphetamine, dorsal striatum, ventral striatum, dopamine synthesis, dopamine degradation, dopamine uptake, dopamine transporter, psychostimulants, striatal dopamine
MeSH terms
Amphetamines, Central Nervous System Stimulants, Animals, Basal Ganglia, Dopamine, Drug Administration Schedule, Drug Interactions, Electric Stimulation, Enzyme Inhibitors, Male, Monoamine Oxidase Inhibitors, Pargyline, Time Factors, Multivariate Analysis, Rats, Sprague-Dawley, alpha-Methyltyrosine, Rats

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