A recent insight has discovered a connection between reward and stress, which offers promise in the treatment of alcohol and drug addiction.
Researchers at the Vanderbilt University Medical Center have found that the brain's chief reward signal, dopamine, works through corticotrophin-releasing factor (CRF)-the main stress signal-to increase the activity of a brain region involved in addiction relapse.
Published by The Journal of Neuroscience, their findings point to new potential targets for dealing with the problem of relapse.
"Even after long periods of abstinence, an individual is at risk for relapse, and stress is what's most frequently cited as initiating that relapse," said Dr. Danny Winder, associate professor of Molecular Physiology and Biophysics in the Center for Molecular Neuroscience and the Vanderbilt Kennedy Center.
Experiments on animals have already shown that a brain region called the extended amygdala, and CRF within it, are involved in stress-induced relapse. Furthermore, alcohol and drugs are also known to increase dopamine levels in this brain region.
However, it was unclear as to what dopamine did in the extended amygdala.
Dr. Thomas Kash, a research instructor in Winder's laboratory, has now found that dopamine increases glutamate signalling in this brain region, and that it requires CRF signalling for this purpose.
Since those findings were based on a lab study, the researchers later involved animals in their research to confirm them.
William Nobis, an M.D./Ph.D. student, injected mice with cocaine and studied signalling in brain slices. His studies confirmed that cocaine engaged the dopamine-CRF signalling cascade that the team had discovered in their lab experiments.
"We think that when an individual takes a drug of abuse or alcohol, it causes a rise in dopamine levels in the extended amygdala, and that likely engages this CRF signalling cascade in this region. That's now activating portions of this brain structure, which then communicate with the core addiction reward circuitry. We believe the dopamine-CRF signalling may be a key initial step in promoting reinstatement behaviour," Winder said.
The researcher said that the novel finding pointed towards a new target to consider for therapeutics that might address stress-induced reinstatement.
"If we can hone in on the mechanisms of this dopamine-CRF interaction, if we can identify the key population of CRF cells, then we could start to think of approaches to silence those cells," Winder said.
He believes that such a therapy can be extremely valuable.
"Essentially all of the pharmacotherapies for addiction to date help people get through the withdrawal phase. There's really nothing available to reduce the likelihood of relapse," he said.
"The recruitment of CRF signalling may be another common feature of drugs of abuse," added the researcher.