Bryan Yamamoto, a School of Medicine professor of pharmacology, is really into drugs — in the best of ways. For two decades, he’s been studying the effects of methamphetamine and ecstasy (MDMA), and his research shows that abuse of methamphetamine leaves important neurotransmitters looking a lot like the neurotransmitters of people who suffer from Parkinson’s and Huntington’s diseases. Now Yamamoto, who notes that the damage to neurotransmitters is long-lasting, is hoping that a better understanding of that process will offer clues to developing new treatments for those diseases.
“We’re looking at the basic science and the pharmacology of these two drugs,” says Yamamoto. “And we’re trying to understand some of the underlying mechanisms that mediate the damage to certain neurotransmitter systems in the brain.”
Yamamoto’s study, in which he administered methamphetamine and MDMA to rats, showed that the two drugs — both classified as amphetamines — affect the brain’s nerve cells differently. Rats that were treated with ecstasy suffered from a 40 to 50 percent depletion of serotonin, a neurotransmitter linked to mood alteration and commonly found in antidepressant medications. Rats treated with methamphetamine suffered from a similar depletion of dopamine, a neurotransmitter linked to movement. Dopamine depletion is known to be the underlying cause of Parkinson’s disease, whose symptoms appear when approximately 80 percent of dopamine-producing cells are damaged.
“Understanding how methamphetamine damages dopamine cells may provide some insight into how dopamine cells die in Parkinson’s disease,” says Yamamoto.
But, he says, because methamphetamine alone does not do the kind of damage to cells that has been seen in Parkinson’s patients, there is no evidence that methamphetamine abuse directly causes Parkinson’s disease.
“It is possible that prior abuse of methamphetamine may accelerate the normal age-related decrease of dopamine cells,” he says. “It could predispose methamphetamine abusers to Parkinson’s disease as they age.”
Yamamoto has also observed that methamphetamine may damage nerve cells that use another neurotransmitter called gamma-aminobutyric acid, or GABA, which helps the body control movement. Depletion of this neurotransmitter has also been observed in patients with Huntington’s disease, a degenerative, hereditary brain disorder affecting movement, emotion, and mental capacity.
To understand the short-term and long-term effects of these drugs, Yamamoto administers methamphetamine and ecstasy to rats in a pattern similar to human drug abusers. While the animals are under the influence of the amphetamines, he takes samples of the fluid surrounding the nerve cells within the brain. He also takes samples of brain tissue days and weeks after the drugs have been administered. Yamamoto has found that when the rats are under the influence of the drugs, they experience an increase in metabolism and a tremendous release of neurotransmitters from neurons, causing hyperactive and hypersensitive behavior. Long-term effects include damage to dopamine and serotonin cells, and in rats treated with methamphetamine, diminished learning ability and memory.
In addition to investigating the effects these drugs may have on neurotransmitters, Yamamoto is exploring how environmental or psychological stressors, known to increase the probability of drug abuse, may contribute to nerve cell damage.
“Once we understand how methamphetamine and MDMA are damaging the nerve terminals,” he says, “novel targets and degenerative processes may be revealed that will allow us to test potentially therapeutic compounds that can be aimed at those targets and interrupt the degenerative processes.”
Yamamoto stresses that these findings are just the beginning and more research is needed.
“We still don’t know the extent of damage produced by these drugs,” he says, “but people are still abusing them. So it’s important to know and relay the message that these are not only addicting drugs, and from that perspective dangerous, but that they could also produce very long-term brain damage.”
Nicole Laskowski can be reached at firstname.lastname@example.org.