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BEYER: For the first couple of years in graduate school it was mainly dopamine. I worked in a lab studying drugs of abuse and, specifically, how cocaine alters dopamine systems in the brain. As the years have gone by at Wyeth, in addition to dopamine, we now routinely monitor norepinephrine, serotonin, and acetylcholine, as well as amino acids such as GABA and glutamate. More recently, we've been exploring neuropeptide systems and by coupling microdialysis with different analytical equipment, for example, mass spec and ELISA-based assays, we are able to capture some neuropeptides in our dialysis samples. ESA: What trends have you observed in microdialysis and how has it changed for you?BEYER: The actual technique of microdialysis has been around for a very long time and all the recent trends have come mainly on the analytical side. Machines are getting more sensitive, and that enables us to look at more chemicals in the same sample. It also allows us to investigate smaller brain areas, where typically there are lower levels of neurotransmitters. These improvements in sensitivity have also allowed better time resolution of samples. For instance, people are routinely sampling on the order of 5 to 15 seconds compared to the 30-minute "bucket samples" usually collected. ESA: Chad, would you categorize your work as mechanistic or behavioral in nature?BEYER; It is certainly more mechanistic than behavioral. This is primarily due to the nature of our work and our focus to discover new drugs to treat psychiatric diseases. But having said that, there is certainly a recent trend to do more dialysis in behaving animals. In our group, for example, we have access to a variety of animal models of disease states - models of depression and anxiety, learning and memory, and pain to name a few - and we are actively pursuing ways to monitor brain chemistry in many of them. So not only have we spent years looking at trying to understand how the brain works and how drugs work, but now, we are moving into correlating neurochemical changes with behavioral states with an eye towards overlaying neurochemical changes with behavior. An example of this is our recent work published in Brain Research showing that in certain pain models, there are specific changes in serotonin levels in the brain stem. The reality is that we will be doing a better job in balancing the mixture of mechanistic and behavioral studies. This should certainly help in our understanding of the brain neurochemistry and new treatment strategies, but it also makes for some great science and papers. ESA: Are there any challenges behavior experiments present that mechanistic experiments do not?BEYER: Clearly! In all of our mechanistic-type studies, the animals are freely moving, but since the experiment is taking place during the light cycle, the animals - for the most part - are sleeping. In our behavior studies, the animals are undergoing operant behaviors like pressing a lever, or in some cases, people have done microdialysis in animals swimming in a maze. Those types of studies are undoubtedly much more technically challenging! ESA: What are the levels of the analytes in both types of experiments? Are there any changes?BEYER: That's a really good question. We haven't looked at them systematically to say that the absolute levels are different in "behaving" animals versus a mechanistic-type study. It would not surprise me, however, if there were differences. I would suspect that there would also be fluctuations in transmitter levels while the animal is behaving. ESA: Do you know of any techniques on the horizon that may supplant microdialysis as technique for in vivo measurements?BEYER: Not really. Clearly techniques such as in vivo voltammetry* are getting a lot more publicity lately. And this is certainly a valuable technique, but I think in terms of supplanting microdialysis, this is unlikely. There is definite value in supplementing neurochemical data with data generated from other techniques, but from my perspective, microdialysis will be around for a while, especially now that the technique is increasingly being done in humans. ESA: Thanks Chad. I really appreciate your time in talking with me.Dr. Beyer's contact information is below: Dr. Chad Beyer *Editor's note: ESA also makes a full range of real-time in vivo voltammetry systems. To request information, click here. |
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