Negative experiences are hardcoded into the human mind. We've evolved to viscerally remember fearful or threatening times, and this threat memory response is important because helps us learn to avoid experiences that could put us in danger. Unfortunately this mechanism is also the source of many anxiety disorders including those founded in significant trauma such as post-traumatic stress disorder (PTSD).
Researchers from University College London and the University of Zurich recently discovered a startling side-effect of the common antibiotic doxycycline – it can disrupt and suppress the formation of fear memories in the brain. This fascinating discovery could not only lead to novel treatments for PTSD, but also offers scientists a clue to how the brain forms lasting fear and threat memories.
The new study builds off decades of evidence pointing toward the role of proteins, called matrix enzymes, in the formation of negative memories. In particular the researchers focused on an enzyme called metalloproteinase 9 (MMP-9). It is still unknown exactly how these enzymes actually aid or inhibit memory formation.
The research team, understanding that there are already clinically approved drugs on the market that inhibit these matrix enzymes, focused on doxycycline, a very commonly used antibiotic that is regularly prescribed for many maladies from acne to general respiratory infections. Doxycycline is known to be able to both inhibit the MMP-9 enzyme and cross the blood-brain barrier, making it a perfect compound for the researchers.
The trial involved 76 healthy subjects who were either given doxycycline or a placebo. They were then subjected to a test where they were shown a range of colors on a computer screen in which one particular color was often followed by a mild electric shock.
A week later the subjects undertook the same test, but this time only a loud sound accompanied the confronting color, not electric shocks. The test was designed to develop a Pavlovian fear response in the subjects when confronted with a certain color. In the second test the subject's fear responses were measured by examining the strength of their eye blinks when faced with the color they previously associated with an electric shock.
This eye-blink based fear response test has been used as a reliable measure of negative memory associations for over 60 years. The compelling results found that the subjects who were initially given doxycycline had a fear response 60 percent lower than those who had the placebo.
"The participants may not forget that they received a shock when the screen was red, but they 'forget' to be instinctively scared when they next see a red screen," explained Professor Dominik Bach, lead author on the study.
Of course this research in and of itself isn't an immediate help to those with PTSD, as it is hard to know when a traumatic event causing long lasting negative memories is about to occur. Although there may be a potential future use in soldiers taking a pill that could inhibit the formation of negative memories before heading out to the battlefield.
Of more interest to Professor Bach and his team is the growing evidence that negative memories can be altered after the initial experience through sophisticated forms of therapy.
"This is called 'reconsolidation', and we now plan to test the effect of doxycycline on reconsolidation of fear memories," said Professor Bach.
As doxycycline is already approved for human use it offers a speedy path through human clinical trials and into mainstream treatment if it is shown to be effective in this reconsolidiation process.
The research was recently published in the journal Molecular Psychiatry.
Source: University College London
