Amphetamine is a widely used psychostimulant drug that is also highly abused, with compounds like methamphetamine being among the most abused psychostimulants globally. The neurological effects of this drug have been extensively studied, revealing its impact on dopamine-related proteins in the brain’s reward center. While the effects of therapeutic doses of amphetamine during pregnancy have been investigated, the long-term effects of exposure to addictive doses during embryonic development are not well understood. Researchers at Florida Atlantic University used the tiny worm C. elegans to explore the mechanisms underlying the long-term effects of amphetamine exposure in embryos.
The study focused on examining changes in the expression and function of two major dopamine-regulating proteins, tyrosine hydroxylase and vesicular monoamine transporter, after exposure to high doses of amphetamine during embryogenesis. These proteins are crucial for dopamine synthesis, storage, and release, influencing various brain functions and behaviors. Results showed that exposure to high doses of amphetamine during embryogenesis led to alterations in gene expression of dopamine-related proteins in adult C. elegans through epigenetic mechanisms. These changes in gene expression translated to behavioral changes in adult animals, making them more susceptible to amphetamine-induced behaviors.
The researchers found that the altered expression of tyrosine hydroxylase and vesicular monoamine transporter caused by continuous exposure to amphetamines during embryogenesis resulted in animals that were hypersensitive to amphetamines in adulthood. This hypersensitivity was evidenced by an increased response to amphetamines in adult animals that had been exposed to the drug during embryonic development. The study also showed that C. elegans is an effective model for studying the long-lasting physiological modifications caused by prenatal exposure to amphetamine, as evidenced by similar findings in mice and rats exposed to the drug.
One advantage of using C. elegans as a model system is that embryos can develop outside the uterus and without maternal care, ensuring that the results are solely influenced by the direct effects of amphetamine exposure during embryogenesis. Behavioral data from the study supported the hypothesis that altered expression of dopamine-related proteins during embryonic exposure to amphetamine leads to hypersensitivity to the drug in adult animals. The researchers hope that their findings will contribute to a better understanding of how amphetamines work in humans, given the conservation of dopaminergic responses to these drugs across species.
The study was published in the International Journal of Molecular Sciences and funded by the National Institute on Drug Abuse, National Institutes of Health. The research team, led by Dr. Lucia Carvelli, included post-doctoral researcher Dr. Tao Ke, undergraduate student Kate E. Poquette, and high school student Sophia L. Amro Gazze. The study’s focus on epigenetic changes and behavioral outcomes after embryonic exposure to amphetamines sheds light on the long-term effects of this drug on brain development and function. The use of C. elegans as a model organism proves useful for investigating the mechanisms underlying amphetamine-induced changes across different species.
