Tiny Worm Reveals Lasting Prenatal Amphetamine Effects

Research has long delved into the impact of therapeutic doses of amphetamine on pregnancy outcomes in humans. However, a comprehensive understanding of the long-term effects of embryonal exposure to addictive levels of amphetamines remains largely uncharted. To address this gap, scientists have turned to a small, yet informative organism: the worm, C. elegans. Researchers from Florida Atlantic University have utilized this organism to elucidate the mechanisms behind prenatal methamphetamine (Meth) and amphetamine exposure, shedding light on their enduring effects.

Amphetamine is well-known as a psychostimulant used to manage various neurological disorders, but it is also one of the most commonly misused drugs globally. Both amphetamine and its derivative, methamphetamine (Meth), are notorious for their potential for abuse. Extensive research has documented the neurological effects from acute and chronic amphetamine use. These studies indicate that proteins involved in the dopamine (DA) system—a neurotransmitter integral to the brain's reward pathways—are either direct targets or are indirectly affected by these drugs.

While therapeutic doses of amphetamine during pregnancy have been explored regarding birth outcomes, the mechanisms that govern the long-term effects of addictive doses on embryonic development have not been fully dissected. Florida Atlantic University researchers are pioneering this field by focusing on the embryonal exposure to high doses of amphetamines and revealing the prolonged effects through C. elegans models. 

The study aimed to determine if exposure to high levels of amphetamine during embryogenesis affected the expression and function of two critical dopaminergic proteins: tyrosine hydroxylase (TH) and vesicular monoamine transporter (VMAT). Both proteins are essential in dopamine synthesis, storage, and release, which are pivotal for brain functions and behavior. 

Published in the International Journal of Molecular Sciences, the study revealed that high doses of amphetamine during embryogenesis alter the expression of genes related to the dopaminergic system in adult C. elegans. These changes occur via epigenetic mechanisms, leading to behavioral modifications in adulthood. Specifically, the animals exposed to amphetamines in their embryonic stage showed increased susceptibility to amphetamine-induced behaviors in later life.

Lucia Carvelli, Ph.D., the senior author and an associate professor of neuroscience at the FAU Harriet L. Wilkes Honors College, emphasized the evolutionary conservation of the dopaminergic system and histone methylation mechanisms across species. This conservation validates the use of C. elegans as a model to study the long-term impacts of prenatal amphetamine exposure, with implications for understanding human physiological responses.

A noteworthy advantage of using C. elegans is that their embryos develop outside the uterus, free from maternal influences. This aspect ensures that the research findings are direct results of biological changes in the embryo rather than potential maternal behavioral or epigenetic modifications.

Behavioral data from the study showed that adult C. elegans exposed to amphetamines during embryogenesis exhibited heightened responses to the drug. This enhanced sensitivity is attributed to the altered expression of TH and VMAT due to the continuous amphetamine exposure during early development.

Dr. Carvelli noted that their findings align with previous animal studies, where mice overexpressing TH displayed increased amphetamine-induced behaviors, and rats chronically treated with amphetamine showed a sustained rise in dopamine reuptake. These results establish C. elegans as an effective and cost-efficient model to investigate the long-lasting physiological changes caused by prenatal amphetamine exposure.

Collaborators on this study included Tao Ke, Ph.D., a postdoctoral researcher in Dr. Carvelli's lab, alongside undergraduate student Kate E. Poquette and FAU High School student Sophia L. Amro Gazze. This research was supported by the National Institute on Drug Abuse, under the National Institutes of Health.

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