Ethanol inhibits dopamine uptake via organic cation transporter 3: Implications for ethanol and cocaine co-abuse
Abstract
Concurrent cocaine and alcohol use is among the most frequent drug combination, and among the most dangerous in terms of deleterious outcomes. Cocaine increases extracellular monoamines by blocking dopamine (DA), norepinephrine (NE) and serotonin (5-HT) transporters (DAT, NET and SERT, respectively). Likewise, ethanol also increases extracellular monoamines, however evidence suggests that ethanol does so independently of DAT, NET and SERT. Organic cation transporter 3 (OCT3) is an emergent key player in the regulation of monoamine signaling. Using a battery of in vitro, in vivo electrochemical, and behavioral approaches, as well as wild-type and constitutive OCT3 knockout mice, we show that ethanol’s actions to inhibit monoamine uptake are dependent on OCT3. These findings provide a novel mechanistic basis whereby ethanol enhances the neurochemical and behavioral effects of cocaine and encourage further research into OCT3 as a target for therapeutic intervention in the treatment of ethanol and ethanol/cocaine use disorders.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 13, 2023
- Source ID
- 10.1038/s41380-023-02064-5
Entities
People
- Diethart Schmid
- Dirk Gründemann
- Felix P Mayer
- G. G. Gould
- Harald H Sitte
- K. M. Clarke
- Lynette C Daws
- M. A. Bowman
- M. Holy
- M. Vitela
- Nikki Clauss
- R. E. Horton
- W. A. Owens
- W. Koek
Organizations
- Austrian Academy of Sciences
- Austrian Science Fund
- National Institutes of Health
- United States Department of Defense
- United States Department of Health and Human Services