June 8, 2013
Study Gives Hope For A Potentially New PTSD Treatment
Lee Rannals for redOrbit.com — Your Universe online
"At first glance, one might infer that the main mechanism by which morphine is working is through pain reduction, but our results lead us to think it could also be affecting the process of fear learning," says senior author Kerry Ressler, MD, PhD, professor of psychiatry and behavioral sciences at Emory University School of Medicine and Yerkes National Primate Research Center.
The compound tested hits one of several molecular buttons in the brain that are pushed by opioid drugs like morphine or oxycodone. SR-8993 was developed by scientists at Miami and Scripps to help treat alcohol and drug addiction originally, and so far the team has not seen any narcotic or addictive effects.
"We hypothesized that the fear and anxiety component of addiction relapse may be related, in terms of brain chemistry, to the anxiety felt by PTSD patients," says co-author Thomas Bannister, PhD, associate director of translational research and assistant professor of medicinal chemistry at Scripps Research Institute in Florida.
The scientists were looking at what genes are activated in the brains of mice after they are exposed to stress. They said they were specifically looking for changes in the amygdala, which is the region of the brain known to be involved in regulating fear responses. Mice exposed to stress become more anxious and tend to freeze in fear, even if there is no "danger," which is a behavior similar to those experienced by humans suffering from PTSD.
The researchers found that exposure to stress particularly affects regulation of the gene Oprl1 in the amygdala. The protein encoded by Oprl1 is part of a family of opioid receptors, which allow brain cells to receive signals from opioid drugs as well as natural compounds produced by the body. The team developed SR-8993 as a compound that activates Oprl1 more than other opioid receptors, thus avoiding narcotic and addictive effects. When they gave the compound to the mice, it impaired "fear memory consolidation."
Mice in the study still were able to become afraid of sounds and shocks, but the fearful memories were not as durable and the mice did not freeze as much in response to the sound alone two days later.
"We think SR-8993 is helping to promote a natural process that occurs after trauma, preventing fear learning from becoming over-represented and generalized," Ressler says. "Our model is that in PTSD, the Oprl1 system is serving as a brake on fear learning, but that brake is not working if prior trauma had occurred."
The team said people with a variation of the Oprl1 gene who experienced childhood abuse tend to have stronger PTSD symptoms. They also have more difficulty discriminating between "danger" and "safety" signals in experiments when they hear startling noises.
"While many hurdles remain for SR-8993 or a related compound to become a drug used to prevent PTSD, these results are important first steps in understanding how such treatments may be effective," Bannister says.
This research comes right in time for National PTSD Awareness Month. According to Oakland County Community Mental Health Authority, one in three troops returning from active-duty are being diagnosed with serious PTSD. Current treatment options for the condition include different forms of therapy, counseling and medication.