It’s bad enough that drug-abusers have to deal with addiction, but according to Donald Kuhn, PhD, they also need to be concerned with the toxic effects that may cause irreversible damage to the central nervous system. Professor of psychiatry and behavioral neurosciences, Dr. Kuhn is examining the mechanisms of commonly abused drugs such as methamphetamines and MDMA, or ecstasy. Although the drugs do not show immediate danger signs, he believes they may damage neurons and cause serotonin deficiencies, which could trigger long-term psychiatric conditions including depression, increased aggression, impulsiveness, hyperactivity, and risk-taking behaviors like suicide or drug use.
With more than $800,000 from the National Institutes of Health/National Institute on Drug Abuse, Dr. Kuhn will investigate "Neurotoxic Amphetamines Radicals and 5HT Neurons." He and his colleagues have genetically-engineered two proteins (trytophan hydroxylase and the 5HT transporter) that are being used as markers for serotonin cells.
"Subjects who’ve used MDMA and methamphetamines show measurable reductions in the function of the serotonin-producing property," said Dr. Kuhn. "Serotonin levels go down and the function of the cell goes down in observable patterns."
Dr. Kuhn is using dopamine deficiency as a model for his research. Many years ago, people who unknowingly took the drug MPTP were developing symptoms identical to Parkinson’s disease. Parkinson’s is characterized by a destruction of dopamine cells, and it turns out that MPTP was destroying dopamine neurons. "The drugs we’re looking at are similar to MPTP, but instead of damaging dopamine cells in the brain, they damage the serotonin cells," said Dr. Kuhn.
By studying the cellular functions, Dr. Kuhn and his colleagues are focusing on the possibility that these drugs somehow produce reactive oxygen species, or possibly nitric oxide, which has damaging potential. "We are also extending our research to determine whether some of these neurotoxic amphetamines are causing certain cells to enter a process of apoptosis. The drug may start a cascade that makes the cells go into a programmed cell death," said Dr. Kuhn.
Collaborators on this project include Drs. Charles Schuster, Susan Land, and Ray Novak, each of whom examines the research findings from slightly different perspectives for a comprehensive study of the drugs’ effects. "We are looking for the mechanistic links between the drug and the loss of serotonin--and what specifically happens in between. In the process of doing so, we hope to come up with new mechanisms by which to protect the proteins, cells and other structures in the brain from this entire destructive process."