Amphetamine exposure during embryogenesis changes expression and function of the dopamine transporter in Caenorhabditis elegans offspring

Ganesh Ambigapathy; Talus J McCowan; Lucia Carvelli

doi:10.1111/jnc.16166

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Amphetamine exposure during embryogenesis changes expression and function of the dopamine transporter in Caenorhabditis elegans offspring

Journal article

Peer reviewed

Amphetamine exposure during embryogenesis changes expression and function of the dopamine transporter in Caenorhabditis elegans offspring

Ganesh Ambigapathy, Talus J McCowan and Lucia Carvelli

Journal of neurochemistry, Vol.168(9), pp.2989-2998

09/2024

DOI: 10.1111/jnc.16166

PMID: 38960397

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Abstract

The dopamine transporter (DAT) is a transmembrane protein that regulates dopamine (DA) neurotransmission by binding to and moving DA from the synaptic cleft back into the neurons. Besides moving DA and other endogenous monoamines, DAT is also a neuronal carrier for exogenous compounds such as the psychostimulant amphetamine (Amph), and several studies have shown that Amph-induced behaviors require a functional DAT. Here, we demonstrate that exposure to Amph during early development causes behavioral, functional, and epigenetic modifications at the Caenorhabditis elegans DAT gene homolog, dat-1, in C. elegans offspring. Specifically, we show that, while embryos exposed to Amph generate adults that produce offspring with no obvious behavioral alterations, both adults and offspring exhibit an increased behavioral response when challenged with Amph. Our functional studies suggest that a decrease in DAT-1 expression underlies the increased behavioral response to Amph seen in offspring. Moreover, our epigenetic data suggest that histone methylation is a mechanism utilized by Amph to maintain changes in DAT-1 expression in offspring. Taken together, our data reveal that Amph, by altering the epigenetic landscape of DAT, propagates long-lasting functional and behavioral changes in offspring.

Amphetamine - pharmacology

Animals

Behavior, Animal - drug effects

Caenorhabditis elegans - drug effects

Caenorhabditis elegans Proteins - biosynthesis

Caenorhabditis elegans Proteins - genetics

Caenorhabditis elegans Proteins - metabolism

Central Nervous System Stimulants - pharmacology

Central Nervous System Stimulants - toxicity

Dopamine Plasma Membrane Transport Proteins - genetics

Dopamine Plasma Membrane Transport Proteins - metabolism

Embryonic Development - drug effects

Epigenesis, Genetic - drug effects

Gene Expression Regulation, Developmental - drug effects

Details

Title: Subtitle: Amphetamine exposure during embryogenesis changes expression and function of the dopamine transporter in Caenorhabditis elegans offspring
Creators: Ganesh Ambigapathy - University of North Dakota
Talus J McCowan - University of North Dakota
Lucia Carvelli - Florida Atlantic University
Resource Type: Journal article
Publication Details: Journal of neurochemistry, Vol.168(9), pp.2989-2998
DOI: 10.1111/jnc.16166
PMID: 38960397
ISSN: 0022-3042
eISSN: 1471-4159
Grant note: R01 DA042156 / NIDA NIH HHS DA042156 / NIDA NIH HHS
Language: English
Date published: 09/2024
Academic Unit: Emergency Medicine
Record Identifier: 9985240897002771

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