Dopamine Receptors Block PTSD in Rats

Post-traumatic stress disorder (PTSD) has presented to the medical, psychological, and health care community one of the most perplexing problems they’ve had to face in many years. A tremendous amount of research is being done on PTSD, because the condition is so widespread, and so heartbreaking. According to a report published by the U.S. Veterans Administration, approximately 30% of the over 800,000 soldiers returning from combat in Iraq and Afghanistan and treated in VA facilities suffer from PTSD. The number of PTSD-related suicides among this population rose in 2012 to over one per day. And post-traumatic stress disorder is not limited to soldiers; it also affects firefighters, emergency care providers, doctors, and ordinary people who have been involved in traumatic accidents or who have been the victims of crime.

The symptoms of PTSD are well documented – those who have the disorder tend to display normal behavior until they are triggered by a memory or a present-day event that causes them to remember the traumatic event and overreact to the memory. The result can be flashback-type memories of the trauma, terrifying dreams at night and frightening thoughts during the day, hyperarousal (being easily startled, feeling tense and on edge, prone to angry outbursts), and avoidance behavior (becoming a “shut in,” avoiding contact with others, and losing interest in activity). What is less well-known is what actually causes PTSD, and how to prevent it or cure it.

A new study in rats may offer some hope

Research conducted by Professor Steven Laviolette and his associates at the University of Western Ontario seems to have offered a new perspective on PTSD. Working with rats, these neurobiologists seem to have identified the area of the brain that is responsible for recalling traumatic memories, and have developed a technique that blocks this memory recall, using a particular dopamine receptor.

Their study pinpoints an area in the prefrontal cortex of the brain in which highly emotionally-charged memories – either negative memories related to trauma or positive memories related to drug addiction that tend to trigger former addicts into relapsing – are stored. They associate such strong memories with the prelimbic cortex, which has been established in previous research as being in charge of the development of learned fear memories and negative behavior conditioning.

In the brain, the neurotransmitter dopamine – and in particular one identified as the D1 dopamine receptor – has been linked to emotional memory function. Laviolette and his co-researchers stimulated this dopamine receptor in rats who had been trained to display behavior similar to the symptoms of post-traumatic stress disorder. The rats had been conditioned to associate a certain smell with receiving an electric shock, and thus display signs of fear – freezing in position, shaking, and remaining motionless – whenever they smelled it. Other rats had been trained to associate another stimulus with pleasant but addicting behavior – getting a dose of morphine. Normally the rats reacted with fear every time they were exposed to the smell, and with anticipation when they were exposed to the morphine stimulus.

By infusing a pharmacological compound into the prelimbic areas of the rats’ brains, the researchers caused the rats to stop displaying this reactive behavior. When the rats’ brains were flooded with the dopamine D1 compound, they experienced the stimuli that previously caused fear or addictive behavior, but no longer reacted to it. What was almost more important is that the drug compound did not remove the memories themselves; when the experiments were repeated with no drug stimulation, the previously trained rats reacted as they had before. When the dopamine receptor was activated, it eliminated only the overreaction to the memory, “without altering the stability of the original memory trace.”

Why this may be important in the treatment of PTSD in humans

Admittedly, this is a preliminary study, and performed on rats, whose memories are far less complex than human memories. However, previous studies and clinical treatment of people with PTSD have used drugs that similarly activate the brain’s dopamine receptors, with positive results. If therapists were able to effectively suppress the PTSD patient’s overreaction to a powerful memory without destroying the memory, it would be beneficial to any treatment program.

Currently part of the problem with treating PTSD has been that when patients are asked to relive the experience in a therapy session, and thus hopefully “work through it,” the results have been the opposite of what was desired – their PTSD became worse, not better. If pharmacological compounds could be developed for humans that don’t affect memories themselves – only the overreaction to the memories – this could hopefully lead to more effective treatment methodologies.

The key finding of this study is that the original memory remains intact. But it loses the power to dictate inappropriate reactive behavior in the PTSD sufferer when the dopamine D1 receptors in a certain area of the brain are stimulated. As Laviolette says, “While it’s true that we learn from negative experiences, PTSD is a pathological form of obtrusive memory recall that devastates the patient psychologically. If we could actively prevent the spontaneous recall of the obtrusive, harmful memories, that would have enormous clinical implications.”

The researchers are hoping that their findings will lead to further research that will reveal drugs that could be used in conjunction with other therapies to reduce the emotional impact of memories associated with either trauma or negative but pleasant behavior such as drug addiction. One can only hope that they are correct in hoping this. The well-being and in fact the very lives of hundreds of thousands of PTSD sufferers is at stake.

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Juliette Siegfried, MPH

Juliette Siegfried, MPH, has been involved in health communications since 1991. Shortly after obtaining her Master of Public Health degree, she began her career at the National Institutes of Health in Bethesda, Maryland. Juliette now lives in Europe, where she launched ServingMed(.)com, a small medical writing and editing business for health professionals all over the world.

Juliette's resume, facebook: juliette.siegfriedmph, linkedin: juliettes, (+31) 683 673 767

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