July 14, 2011
CHARLESTON -- Imagine if Charlie Sheen were able to break the link his brain makes every time he sees triggers in his environment that induce a substance abuse relapse. He might still have his hit show and his wife.
In an article published in the July 15 edition of Science, MUSC and NIH researchers report the discovery of a new brain circuit that is responsible for connecting contextual, or environmental, cues and stimuli with the perceived reward for responding to those cues. This discovery is important for developing new therapies to treat recovering drug addicts, people suffering from certain mental illnesses such as schizophrenia, or people who live with learning disorders. It also sheds light on the brain system responsible for allowing people to adapt to changes in their environments over time.
Gary Aston-Jones, Ph.D., MUSC Neurosciences Professor and the William E. Murray SmartState Endowed Chair in Neuroscience, worked with first author Alice Luo on the project prior to her employment as a researcher with the National Institutes of Health: "Context is important in all aspects of life. Everything we do is guided by the context in which we find ourselves. For example, the environment (or context) where a person previously acquired drugs becomes a major trigger for relapse in addicts."
Like many addicts, Sheen's environment is full of constant reminders about his prior drug-taking. This new research shows how a part of his brain (the hippocampus, an area of the brain responsible for recognizing and processing the environment around you), links to the dopamine system (VTA), an area responsible for "expectation of reward", via a relay called the septum. When the hippocampus activates the VTA via this circuit, it directs Sheen to seek the reward that he will get from the drug. For example, an addict might typically go to a certain neighborhood to buy drugs and get his fix. If he is in a similar neighborhood, a message is relayed from the hippocampus to VTA, "Hey! Look where I am! I got drugs in a place like this before! Go get a fix. Remember, a fix feels good, go get a fix..." According to Aston-Jones, this circuit can relay this information to the dopamine reward system very quickly and strongly. "In an experienced addict, this can overpower other more normal behavior," he said.
Using rodent models, Luo, Aston-Jones and their colleagues inactivated the circuit by alternately blocking the circuit's path in the hippocampus, septum or within the dopamine system. Blockade of this circuit at any point dramatically decreased the ability of a drug environment to cause drug-seeking in rats.
One of the parts of this new circuit, the lateral septum, was a hot area of research in the 1950s because it was the first brain region found where electrical stimulation caused strongly rewarding effects. This "electrical brain self-stimulation" phenomenon was discovered by James Olds, who was Aston-Jones's first thesis advisor in the 1970s. The present research was carried out by Luo who did her thesis work with Aston-Jones. Another project conducted by graduate student Greg Sartor in the Aston-Jones lab at MUSC also shows the lateral septum to be important in reward processing. "Our research brings the septum full-circle," Aston-Jones said. "It confirms Olds' initial observations and identifies the circuit it is involved in to cause these reward effects".
The identification of this circuit shows researchers and clinicians brain areas to target to treat addiction. For example, deep brain stimulation (DBS, a procedure that neurosurgeons specialize in at MUSC) turns off an area of the brain when it is administered. This new research indicates that DBS in the septum may be a new avenue for treating intractable addiction to drugs or alcohol. This research may also be relevant to natural reward craving as well, such as what occurs for food in some obese individuals.
To learn more or for a full copy of the article entitled "Linking Context with Reward: A Functional Circuit from Hippocampal CA3 to Ventral Tegmental Area," go to http://www.sciencemag.org/.
Founded in 1824 in Charleston, The Medical University of South Carolina is the oldest medical school in the South. Today, MUSC continues the tradition of excellence in education, research, and patient care. MUSC educates and trains more than 3,000 students and residents, and has nearly 11,000 employees, including 1,500 faculty members. As the largest non-federal employer in Charleston, the university and its affiliates have collective annual budgets in excess of $1.7 billion. MUSC operates a 750-bed medical center, which includes a nationally recognized Children's Hospital, the Ashley River Tower (cardiovascular, digestive disease, and surgical oncology), and a leading Institute of Psychiatry. For more information on academic information or clinical services, visit www.musc.edu or www.muschealth.com.