During pregnancy, scientists have studied the impact of therapeutic doses of amphetamine on birth outcomes in humans. However, there has been limited exploration into the mechanisms that cause long-term effects from embryonic exposure to addictive doses of amphetamine. Researchers have used a small worm to uncover the mechanisms of embryonic exposure to methamphetamine (Meth) and amphetamines, which are psychostimulants used to treat various brain dysfunctions. Amphetamine is a psychostimulant that has been used to treat a variety of brain dysfunctions, but it is also highly abused.
Amphetamine and its derivatives, including methamphetamine, are highly abused psychostimulants worldwide.
Research has extensively explored the neurological impacts of acute or chronic amphetamine use. Multiple studies have demonstrated that proteins involved in dopamine (DA) synthesis, storage, release, and reuptake, a neurotransmitter central to the “reward” center, are either directly targeted or indirectly impacted by these drugs.
Studies have also looked into the effects of therapeutic doses of amphetamine during pregnancy on birth outcomes.
The long-term effects of embryonal exposure to addictive doses of amphetamine in humans have not been thoroughly studied. Researchers at Florida Atlantic University used a tiny worm, C. elegans, to investigate the mechanisms within the embryo after exposure to high concentrations of amphetamines and discovered their long-lasting effects. The study examined whether exposure to high doses of amphetamine throughout embryogenesis causes changes in the expression and function of two major dopaminergic proteins, tyrosine hydroxylase (TH).The study found that high doses of amphetamine during embryogenesis can alter the expression of specific genes in the dopaminergic system in adult C. elegans through epigenetic mechanisms. This results in changes in behavior in adult animals, affecting the synthesis, storage, and release of dopamine, which is critical for various brain functions and behaviors. The findings were published in the International Journal of Molecular Sciences.C. elegans that were exposed to amphetamine during embryonic development showed increased vulnerability to amphetamine-induced behaviors. Lucia Carvelli, Ph.D., a senior author and associate professor of neuroscience at FAU Harriet L. Wilkes Honors College and a member of the FAU Stiles-Nicholson Brain Institute, explained that the dopaminergic response to amphetamines and the mechanisms involved in histone methylation are highly conserved across different species, which is why C. elegans was used to study the long-term effects of embryonic exposure to amphetamines. The use of C. elegans as a model system was important for understanding the workings of amphetamine, even though the ultimate goal is to gain insights into how amphetamine affects human behavior.The model used by the researchers has the advantage of allowing C. elegans embryos to develop outside the uterus and without maternal care. According to Carvelli, the results were not affected by potential amphetamine-induced epigenetic or behavioral changes passed down through maternal care, but were a direct result of biological changes in the embryo. Behavioral data from the study indicates that adult animals show an increased response to amphetamines after being exposed to amphetamine during embryonic development. This indicates that the changed expression of TH and VMAT is responsible.Exposed to amphetamines during embryogenesis, animals develop hypersensitivity to amphetamines.
“Our results align with findings showing that mice overexpressing TH show increased amphetamine-induced behaviors, and that rats treated with amphetamine long-term experience a sustained increase in striatal dopamine reuptake. Our research establishes C. elegans as a cost-effective model to study the lasting physiological changes caused by prenatal exposure to amphetamine,” said Carvelli.
Tao Ke, Ph.D., a post-doctoral researcher in the Carvelli lab, is a co-author of the study.; Kate E. Poquette, a student at FAU and Sophia L. Amro Gazze, a student at FAU High School.
This study was supported by the National Institute on Drug Abuse, National Institutes of Health (grant No. DA042156), which was given to Carvelli.
