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Researchers discover brain circuit vital in addiction

Spotlight in the Lab

Imagine if actor 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 National Institutes of Health (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.

Brain artGraphic provided by Emma Vought, Neurosciences

Gary Aston-Jones, Ph.D., MUSC neurosciences professor and the William E. Murray SmartState Endowed Chair in Neurosciences, worked with first author Alice Luo, Ph.D., on the project prior to her employment as a researcher with NIH: "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."

The research
This new research shows how a part of the brain (the hippocampus, an area of the brain responsible for recognizing and processing the environment), 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 people to seek the reward they 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 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 student Greg Sartor in the Aston-Jones lab also shows the lateral septum to be important in reward processing. "Our research brings the septum full-circle," Aston-Jones said. "It confirms Olds' 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 research indicates that DBS in the septum may be a new avenue for treating intractable addiction to drugs or alcohol. This research may be relevant to natural reward craving, such as what occurs for food in some obese individuals.

For a copy of "Linking Context with Reward: A Functional Circuit from Hippocampal CA3 to Ventral Tegmental Area," visit


Friday, July 22, 2011

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