Bob Hitzemann, PhD, has devoted his four-decade career to understanding how genes regulate complex behaviors, particularly drug-induced behaviors. To put his research experience into perspective for the hundreds of people that attended his March Marquam Hill Lecture, he pointed out that when he began his career, there were just five known neurotransmitters. The list excluded GABA (gamma aminobutyric acid), glutamate and about 50 active neuropeptides, plus gases which act as neurotransmitters. “We had very limited knowledge,” he said.

His very first paper was published in 1970, and although it wasn’t about drug abuse, he used it to prove a point about technology. The paper relied on a $5,000 spectrophotometer to measure the fluorescence of molecules in a diluted solution. “Technology has really driven the field forward,” said Dr. Hitzemann. “Without the advances in technology, we’re not going to make advances in neuroscience and specifically drug abuse [research].”

Dr. Hitzemann is Professor and Chair of the Department of Behavioral Neuroscience. Before joining OHSU in 2000, he was on the faculty of SUNY at Stony Brook, New York. He obtained his PhD in Pharmacology at the University of California, San Francisco. He was also an Assistant/Associate Professor at the University of Cincinnati, where he was first introduced to translational research when working with psychiatrist colleagues. “I can’t tell you how important this was for me for the episodes of my career that would come later.”

His research has been influential in understanding alcohol and drug abuse. When a drug is abused – be it cocaine, alcohol or heroin – the effect on the dopamine system is a down-regulation of receptors. “The brain is acting exactly the way it should in response to the release of dopamine,” he said. “How does a drug abuser interpret that? They simply take more drug to overcome this adaptive effect.”

One of his most important studies looked at cocaine abusers among a population of veterans. The findings – illustrated here and “reproduced thousands and thousands of times” – suggest permanent changes in the brains of cocaine addicts. Even four months after stopping cocaine use, dopamine receptors had not recovered as the researchers had predicted. Dr. Hitzemann’s own brain was scanned and included as the normal control in this image.

During the lecture, Dr. Hitzemann also spoke about colleagues who influenced the direction of his research. He met John Crabbe, PhD, now Director, Portland Alcohol Research Center, at a conference in Puerto Vallarta, Mexico, in 1986. Dr. Crabbe was the person who got him interested in mouse genetic research and how genes play into drug abuse.

In 1991, at a meeting organized by Dr. Crabbe, he met Dr. Gerald McClearn, an investigator who first discovered in the 1950s that different strains of mice respond differently to alcohol. He asked Dr. McClearn, “What would you do if you were me to make the biggest influence on behavioral genetic research? He said, ‘We need a new line of mice that we can selectively breed from.’”

Dr. Hitzemann followed Dr. McClearn’s advice. Those mice are still alive at OHSU, now in generation 70, and they have been used all over the world to map behavioral phenotypes. About 15 years later, this led to the discovery of the gene involved in the processing of neuropeptides.

During a question-and-answer session with the audience, Dr. Hitzemann was asked what he hopes for the future of drug abuse and subsequent treatments. “I hope we have drugs that repair the brain,” he said. “Therapies like that will be amazingly effective and will help drug addicts cope better with all the other things going on in their lives.”

























Figure 1
Volkow, N. D., Fowler, J. S., Wang, G.-J., Hitzemann, R., Logan, J., Schlyer, D. J., Dewey, S. L. and Wolf, A. P. (1993), Decreased dopamine D2 receptor availability is associated with reduced frontal metabolism in cocaine abusers. Synapse, 14: 169–177. doi: 10.1002/syn.890140210

Pictured above: Bob Hitzemann, PhD