New Research Examines Effects of Amphetamines on Gene Expression

Doctors, scientists and researchers have been trying for decades to understand addiction. In gaining a better understanding, they could more easily develop more effective treatments and even successful approaches to prevention. A different type of study has been completed and Science Daily has the latest report.

In studying zebrafish, researchers have determined the effects of amphetamines on gene expression. The new study helps to provide clues to the genetics underlying susceptibility to addiction by describing the nad zebrafish mutant. This particular organism cannot feel the rewarding effects of the drugs.

An international team of researchers worked together to carry out the experiments. Katharine Webb, from the German Research Center for Environmental Health, Helmholtz Zentrum München, and a researcher said, “Addictive drugs all trigger a sequence of widespread long-lasting consequences on brain physiology, most of which are only partially understood.

Because a major step in the development of addiction is the switch from drug use to drug abuse, we aimed to gain insight into the mechanisms triggering the initiation of addictive behavior,” Webb added.

Webb and the rest of the team used the mutagenic chemical ENU to generate hundreds of mutant zebrafish to breed a line that did not respond to amphetamine administration. The fish appeared to be normal in all other ways.

In comparing the drug-proof nad mutants to fish with a normal response, the researchers discovered a set of 139 genes that respond inappropriately to amphetamine in nad mutants.

The gene set also displayed a striking enrichment in transcription factors that are specifically known for their involvement in brain development. In addition, several of these genes were expressed in neurogenic domains of the adult fish brain.

The researchers noted, “These factors, which are also dramatically down-regulated by amphetamine, can serve as valuable new entry points into studying the link between adult neurogenesis and addiction.”

Researchers hope these results will identify a new network of coordinated gene regulation to influence the response to amphetamine and could underlie the susceptibility to addiction.