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Dopamine Lets Bad Experiences Linger
Date:8/22/2009

Interfering with neurotransmitter prevented memories from forming, taking root, study finds

FRIDAY, Aug. 21 (HealthDay News) -- Imagine being able to prevent the formation of traumatic memories before they take root in the brain.

That's the promise of a new study on long-term memory formation in rats -- assuming the findings can be applied to humans, that is.

Martin Cammarota, of the Pontifical Catholic University of Rio Grande do Sul, Brazil, with colleagues at the University of Buenos Aires, Argentina, demonstrated in rats that it is possible to disrupt long-term storage of certain memories, assuming that intervention occurs at the right time.

"These investigators have identified specific mechanisms and brain areas, and a definite time frame for conversion of short-term memories into long-term memories, and they are actually able to influence that process," said Dr. Randall Marshall, medical director of clinical research at the pharmaceutical company, Sepracor, which specializes in drugs that act on the central nervous system.

Specifically, Cammarota and his team put rats through what's called an inhibitory avoidance task. In this test, a rat is given an electrical shock through the foot. It is then tested periodically to determine whether it remembered the event. Essentially, if the memory becomes "consolidated" -- that is, written to the brain's "hard drive" -- the animal will hesitate to place its foot on the electrified surface (a time delay called "latency").

In this study, when given a relatively weak electrical shock, the animals tended to quickly forget the experience, placing their feet back on the electrified surface with little hesitation seven days after the initial shock. By contrast, rats given a more powerful shock remembered the experience longer, demonstrating latency up to 14 days later.

The team then attempted to prevent long-term memory formation by interfering with the neurotransmitter dopamine, which is associated with pleasurable and painful stimuli. If a blocker for the dopamine receptor was injected into the hypothalamus of the brain 12 hours after the shock -- but not immediately after the shock or nine hours later -- the rats effectively forgot about the experience: seven and 14 days after the shock, they exhibited little to no latency. Conversely, if a dopamine receptor activator was injected 12 hours following a weak shock, the rats remembered the experience as if they had received a strong shock.

In other words, at a specific point following the shock, the researchers could pharmacologically alter these animals' brains, causing them either to forget the traumatic experience, or to remember it more strongly.

The implication, said Roy Wise, chief of the behavioral neuroscience branch in the Intramural Research Program at the National Institute on Drug Abuse, is that "the memories we thought were solid and accurate are not."

The effect depended on the activity of a specific brain protein called BDNF, and on interaction of the hypothalamus with another brain region called the ventral-tegmental area.

"I think it's a really exciting study," said Philip Corlett, of the University of Cambridge and Yale University. "Understanding more about how long-term memories are formed may have huge implications for psychiatric diseases, which often are diseases of memory."

Assuming the results can be replicated in humans -- which is by no means certain, given that the rats were treated via shunts in the brain, a delivery method unlikely to be used in humans -- potential applications run the gamut from boosting learning to ameliorating the effects of psychiatric diseases. But perhaps the most obvious human application involves post-traumatic stress disorder (PTSD).

"If you could get to somebody soon after the traumatic experience, you might be able to interfere with this consolidation process and reduce the risk of PTSD," said Marshall.

That is not the same as "erasing" memories, as in the 2004 movie Eternal Sunshine of the Spotless Mind. Instead, this research suggests it is possible to prevent memories from forming in the first place, or at least from being stored long-term.

Normally, of course, an individual wants to retain his or her memories -- especially powerfully pleasurable or painful memories, which are the ones associated with dopamine release. "You want to remember where the lion's den was, so you don't go down that pathway again in the jungle," observed Marshall.

For those suffering from PTSD, however, those memories are more than mere reminders; they begin to interfere with normal everyday life.

"That's the potential application," said Marshall, "whether we can understand these brain processes well enough to protect people from these memories becoming so powerful and so deeply consolidated in the brain that they become a source of suffering."

More information

For more information on PTSD, visit the U.S. National Institute of Mental Health.



SOURCES: Randall Marshall, M.D., medical director, clinical research, Sepracor; Philip Corlett, Ph.D., Parke-Davis Exchange Fellow in Biomedical Sciences, University of Cambridge & Yale University, Department of Psychiatry, Connecticut Mental Health Center, New Haven, Conn.; Roy Wise Ph.D., branch chief, behavioral neuroscience branch, intramural research program, National Institute on Drug Abuse, National Institutes of Health, Bethesda, Md.; Aug. 21, 2009, Science


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