This week we profile a recent publication in Nature from first author Dr. Daniel Castro (pictured, second row from bottom, left) and the laboratory of Dr. Michael Bruchas (top row, second from left) at UW.
Can you provide a brief overview of your lab’s current research focus?
We focus on neuromodulatory processing in the brain, as it relates to affective and stress behaviors. Within these psychological domains, we are particularly interested in the role of a particular type of receptor called G-protein coupled receptors. This class of receptor is important for modulating how neurochemical signals in the brain impact different brain circuits that mediate motivation, stress, and addiction. These receptors represent one of our largest possible places for which to develop new therapies for a variety of neurological and psychiatric diseases. Our efforts to understand them at a systems and cell biology level will facilitate the development of new pharmacological approaches.
What is the significance of the findings in this publication?
These findings pin down a major biological mechanism through which opioids act to potentiate motivated behaviors. While most people are familiar with exogenous opioid drugs like morphine or fentanyl, it turns out that we also have an endogenous opioid system. While neuroscience research has identified the nucleus accumbens as an important mediator of opioids on reward behaviors until now we did not have the required technology to address the deeper biological questions. These include: where are the opioid receptors located? When do they get activated? What endogenous opioid peptide acts on these receptors? By understanding the underlying blueprint for how these endogenous systems function, we may be able to develop better therapeutics.
What are the next steps for this research?
While the results of these experiments provided answers to questions that have been around for decades, they also inspire new ones. Moving forward, we could evaluate how this particular circuit is involved in other types of motivated behaviors, whether it modified exogenous drug reward, or examine how this circuit interacts with other important brain systems. Regardless of which projects we pursue in the future, it cannot be overstated how important it is to have both clinically driven science, as well as fundamental scientific investigations, like the study we published. These two approaches work together to serve deep insights into how the brain works, we look forward to pursuing both avenues of study.
If you’d like us to mention your funding sources, please list them.
This work was funded by the National Institute on Drug Abuse, National Insitute of Stroke and Neurological Disorders, National Institute of Diabetes and Digestive and Kidney Disorders, Brain and Behavior Research Foundation, and the Mallinckrodt Endowed Professorship. Grant Numbers: NS007205, DA043999, DA049862, DA051489, DA051124, DK121883, DA041781, DA042499 DA045463, DA032750, DA038168, DA048736, R37DA033396, R61DA051489, P30DA048736.
