August 20, 2013
Distinguished Professor of Neurobiology Paul Garris is working to create a “smart device” in the hopes of stifling the rewarding properties of abused drugs.
Garris is part of a duo that recently received a $390,000 grant from the National Institute on Drug Abuse, which will help design a device aimed at curbing the brain’s response to amphetamines by controlling levels of dopamine.
In many ways, dopamine is a messenger within the brain, giving it signals about movement, cognition and motivation. It is the motivation aspect that is connected with drug addiction, noted Garris. “Dopamine neurons behave in a particular way when involved in motivation. They have these chemical bursts of activity called ‘dopamine transients’ that help us learn how to obtain natural rewards.”
Much like Pavlov’s dog responded to the bell that signaled food, dopamine neurons learn to respond to food cues by generating a burst of activity. “In the natural order of business, that’s how we learn how to find food,” said Garris. “Drugs of abuse trick our brains and hyper-activate these dopamine signals, more than the natural rewards. So the brain pays more attention to the cues for getting drugs, which can lead to addiction.”
For decades, Garris has studied dopamine and its impact on the brain. He created a device to measure levels of dopamine in the brain that was adopted and further developed by the Mayo Clinic. A version of it is now used for neurochemical monitoring in patients during neurosurgery.
Now Garris wants to go beyond merely measuring dopamine. Teaming up with engineer Pedram Mosheni of Case Western University, Garris is designing devices that will act as “a neurochemical thermostat.”
“In theory, our device will not only measure these bursts of chemical activity, but determine if they are too high. Then it will engage a circuit that will ‘quiet’ the dopamine neuron with negative feedback,” said Garris, who noted the device will stimulate a brain pathway that inhibits dopamine neurons.
Garris said the device will have to be sensitive in order to preserve a delicate balance. “You need dopamine neurons for normal behavior. You cannot just shut them off,” he said. “So you cannot go too high or too low. Ultimately what we are trying to do is make drugs less appealing, and preserve normal function.”
This is the fourth federal grant supporting Garris’ collaboration with Mosheni. Together, they are developing an application-specific integrated circuit, which Garris calls the “brains” of the smart device. “My original design was about the size of a pack of Wrigley’s gum. As an engineer, Pedram has been able to get the design down to a microchip that could be implanted in the body and connected to electrodes inserted in the brain,” he said.
Currently the device is in the development and research stage, though in the future Garris said it may have human applications. Already the field is seeing “deep brain stimulation” or DBS neurosurgeries, where high-frequency stimulation is applied directly to the brain to treat pathologies. “This approach is known as ‘open loop,’ meaning the neurosurgeon begins the stimulation, and it continues until the surgeon stops or alters it. We are trying to control the stimulator automatically using chemical signals as feedback, and close that loop with the device,” said Garris.
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