September 2009


by James J. Galligan, Ph.D., Associate Chair,
Department of Pharmacology and Toxicology

A few weeks ago, I discussed methlymercury contamination of freshwater fish in lakes scattered around the United States.  This topic was of interest because of the local expertise here in Pharmacology and Toxicology on methylmercury induced neurotoxicity.  Well, Michigan State University also has an outstanding research and training program in environmental toxicology (http://cit.msu.edu/) and another news item caught my attention that was highly relevant to the environmental toxicology expertise here at MSU (http://www.google.com/hostednews/ap/article/ALeqM5gqrMC7NvYKe4jGTjLIZM-jRqp-7QD9AVQQK04).

Cyanobacteria in Pool

Cyanobacteria in Pool

Cyanobacteria (blue green algae) blooms are contaminating many freshwater lakes in the U.S.  These algae blooms are unsightly, smelly and potentially deadly, particularly for pets.  Warm dry weather coupled with fertilizer run-off from farms are the main culprits leading to prolific growth of cyanobacteria.  The resulting blue-green sludge piles up on lakeshores and dying and decaying bacteria cause the foul odors.  This ruins the aesthetics of the lakes and certainly reduces the enjoyment for lake front property owners.  However, the real danger comes from the toxins produced by these bacteria.

Cyanobacteria produce two types of toxins: alkaloids and the peptide microcystins.  The alkaloids include saxitoxin, a sodium channel blocker that is a neurotoxin.  Microcystins are small peptides (7 amino acids) and they are predominately liver toxins.  Ingestion of contaminated water results in high levels of microcystin exposure to the intestine and then the liver.  Microcystins are phosphatase inhibitors that disrupt the protein structure of cells in the liver ultimately leading to death of liver cells (hepatocytes) and liver bleeding.  Human poisoning with cyanobacteria-produced toxins is rare because humans (at least most of them) are smart enough not to ingest the foul looking and foul smelling cyanobacteria contaminated water.  However, livestock, or the pet dog may not be so clever or lucky.

The other issue is the wildlife (waterfowl, fish, amphibians) that inhabit the contaminated lakes and who can not avoid exposure to the toxins.  Typically, the algae blooms are short lived and dissipate with rain or a nice breeze.  However, the kill off of the local inhabitants of the lake can far outlast the algae bloom and therefore the effects on the overall health of the lake can also be long lasting.

by James J. Galligan, Ph.D., Associate Chair,
Department of Pharmacology and Toxicology

The fall semester has started at MSU and I am fully immersed in a course I teach on drug abuse and  jama-logoaddiction.  This has brought my focus to news items related to drug addiction and its treatment. An article published in the September 9 issue of the Journal of the American Medical Association provides some interesting new data that may be related to drug addiction, motivation and mental illness.

Attention deficit hyperactivity disorder (ADHD) is an illness in which some children and adults have difficulty focusing on single tasks. It has always been puzzling that the drug most commonly used to treat ADHD is an amphetamine-like drug called methylphenidate (Ritalin). Why would we use a stimulant drug to treat an illness already associated with hyperactivity? Well, the study referenced above may have helped solve this puzzle.

Positron Emission Tomography (PET)

Positron Emission Tomography (PET)

The investigators used positron emission tomography to study the activity of dopamine neurons in the brains of normal subjects and ADHD patients. Specifically, they looked at dopamine neurons in the mesolimbic dopamine pathway. The mesolimbic dopamine pathway is part of the brain’s reward system as it becomes active when we perform enjoyable tasks, such as eating, or when we feel good about an accomplishment. This is also the brain pathway that is hijacked by addictive drugs like amphetamine, cocaine, heroin and nicotine. The study revealed that ADHD patients had impaired dopamine signaling in the mesolimbic dopamine pathway. This would cause ADHD patients to experience reduced rewards for performing tasks successfully and perhaps this is why ADHD patients have difficulty concentrating and completing tasks.

The results of the study are important for a number of reasons. Firstly, the results provide new information about the abnormalities in brain function that may be responsible for ADHD. Secondly, these data help to explain the paradoxical benefits of a stimulant drug for treatment of hyperactivity. As methylphenidate causes an increase in dopamine mediated neurotransmission, methylphenidate may boost activity in the endogenous reward system making it easier for the ADHD patient to experience the reward associated with task completion. Lastly, these data may also help to explain the increased incidence of drug addiction and obesity in ADHD patients. If their endogenous reward system is impaired, these subjects may seek out addictive drugs which activate the reward pathways. This might also explain the overeating that leads to obesity in some ADHD patients.

If there is reduced reward associated with eating, the ADHD patient might overeat in an effort to compensate for the reduced reward associated with feeding. This new information may not only help to treat ADHD, it may also lead to new treatments for drug addiction and obesity.

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