Ceramide-Induced Alterations in Dopamine Transporter Function
Abstract
The purpose of this study was to determine the effects of ceramide on dopamine and serotonin (5-HT, 5-hydroxytryptamine) transporters. Exposure of rat striatal synaptosomes to C2-ceramide caused a reversible, concentration-dependent decrease in plasmalemmal dopamine uptake. In contrast, ceramide exposure increased striatal 5-HT synaptosomal uptake. This increase did not appear to be due to an increased uptake by the 5-HT transporter. Rather, the increase appeared to result from an increase in 5-HT transport through the dopamine transporter, an assertion evidenced by findings that this increase: (1) does not occur in hippocampal synaptosomes (i.e., a preparation largely devoid of dopamine transporters), (2) occurs in striatal synaptosomes prepared from para-chloroamphetamine-treated rats (i.e., a preparation lacking 5-HT transporters), (3) is attenuated by pretreatment with methylphenidate (i.e., a relatively selective dopamine reuptake inhibitor) and (4) is inhibited by exposure to exogenous dopamine (i.e., which presumably competes for uptake with 5-HT). Taken together, these results reveal that ceramide is a novel modulator of monoamine transporter function, and may alter the affinity of dopamine transporters for its primary substrate.
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Increased Cer concentrations may contribute to the progression of depression.
“Increased Cer concentrations may also contribute to the progression of depression, as Cers may affect dopamine transporter function by decreasing dopamine transport and increasing 5HT transport [39].”
From Lipids in Psychiatric Disorders: Functional and Potential Diagnostic Role as Blood Biomarkers (2024) · cites this paper as [39]
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- Authors
- Riddle, E. L., Rau, K. S., Topham, M. K., Hanson, G. R., & Fleckenstein, A. E.
- Affiliations
- University of Utah (US)
- Corresponding author
- Fleckenstein, Annette E
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2003-01
- Volume
- 458
- Issue
- 1-2
- Pages
- 31-36
- ISSN
- 0014-2999 (ISSN-L)
- OpenAlex
- W2017922840
- Cited by
- 37
- References
- 24
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 2 · 2013: 1
- FWCI
- 0.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5f31da014475-02)
- National Institute on Drug Abuse (R01DA000869, DA 00869, DA 04222, DA 11389, K05DA000378, DA00378, DA14475, R01DA004222)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- ceramide, dopamine transporter, serotonin transporter, dopamine uptake, serotonin uptake, striatum, synaptosomes, monoamine transporters, C2-ceramide, methylphenidate, dopamine uptake inhibition, substrate affinity
- MeSH terms
- Animals, Binding, Competitive, Ceramides, Cocaine, Dopamine, Dose-Response Relationship, Drug, Male, Membrane Glycoproteins, Methylphenidate, Nerve Tissue Proteins, Serotonin, Synaptosomes, Tritium, Rats, Sprague-Dawley, Membrane Transport Proteins, Dopamine Plasma Membrane Transport Proteins, Rats
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