PROVIDENCE, R.I. [Brown University] — Brown University neuroscience professor Gilad Barnea will receive a nearly $1.3 million, four-year federal grant toward development of a method to selectively monitor the activation of each of the five receptors for the neurotransmitter dopamine in the brain.
If he succeeds, the achievement could lead to more targeted treatments for several mental illnesses and a number of other diseases.
“It can make a big impact on the development of new drugs for multiple disorders,” said Barnea, assistant professor of neuroscience.
The award, known as a EUREKA grant, is funded by the National Institutes of Health’s National Institute of Mental Health. EUREKA grants — for Exceptional, Unconventional Research Enabling Knowledge Acceleration — are part of a new NIH initiative, less than two years old, that funds innovative, high-risk/high reward research.
Barnea will use the funding to develop a method for selectively monitoring the activation of each of the five dopamine receptors in the brain, without interference from the others. Such an advance matters because often several different receptors, beyond the one that physicians and scientists wish to target, respond to the same drug. This imperfect process leads to side effects from drugs that could be more beneficial if they worked in a more precise way. The membranes of all the cells in the body contain many receptors that receive signals from outside the cell and translate them into various responses inside the cell. These responses can include alteration of gene expression.
The ability to monitor the activation of a single dopamine receptor would be crucial for developing more precise and effective treatments for several mental disorders such as schizophrenia, bipolar disorder and attention deficit hyperactivity, as well as for other disorders such as addiction, Parkinson’s disease and hypertension.
The long-term implications of Barnea’s success are even larger. Dopamine receptors belong to the family of G Protein Coupled Receptors (GPCRs — the largest family of receptors in the body) that respond to a variety of stimuli including various hormones and neurotransmitters. Due to their pivotal role controlling a variety of physiological signals, GPCRs are common targets for pharmaceutical therapies, including treatments for psychiatric conditions, hypertension, asthma, allergies, peptidic ulcers and certain cancers. Barnea believes that the method, once developed and proven successful, could be applied to other types of GPCRs. If so, the concept could have a broad impact both on the understanding of the physiology of these receptors, and on the development and testing of specific drugs for a wide range of illnesses, all with fewer side effects.
For the study, Barnea and his lab plan to develop several strains of mice in which the specific types of dopamine receptors will be monitored.
Barnea said he developed the idea that led to the EUREKA award from his main focus on understanding how the brain analyzes the information it receives from the nose to perceive scents.
To do this, Barnea has been developing a new system for labeling neural circuits across synapses in the brain. Some elements of this system, he said, could be reconfigured and modified to address the newer question about dopamine receptors and other GPCRs.