Pregabalin & L-Theanine Prophylactic Effects on PTSD Behavior and Gene Expression

Post-traumatic stress disorder (PTSD) occurs in 30% of Veterans from the wars in Iraq and Afghanistan and is closely linked and a probable sequelae to traumatic brain injury (TBI), the “signature injury” of these wars. Although effective treatment of PTSD is crucial, it would be more advantageous to prevent PTSD. However, there are NO known interventions that prevent the development of PTSD. Pregabalin (PGB) has shown to decrease excitatory neurotransmission in the brain and may also decrease the changes associated in the development of PTSD. Similarly, L-theanine (L-Th), a major compound found in the herbal supplement green tea has been found to decrease anxiety and locomotion and may have positive effects in the prevention of PTSD. This research proposal will investigate PGB and L-Th effects on neurobehavioral and specific gene expression in a PTSD rodent model. This is the first innovative prospective experimental study that will investigate the possible prevention of PTSD by PGB and L-Th. The aims of this study are to determine if prophylacticly administered of PGB or L-Th prevent PTSD development in the rodent model. Specifically, the aims are as follows: 

1. Determine the effects of PGB and L-Th on anxiety and locomotion

2. Determine the effects of PGB and L-Th on hyperarousal/enhances startle

3. Determine the effects of PGB and L-Th on memory 

4. Determine the effects of PGB and L-Th on depression

5. Determine the effects of PGB and L-Th on gene expression in the brain

The study design integrates neurobehavioral effects with two major neurotransmitter systems and their gene expression in a rodent model of PTSD. The rationale for this proposed research is based on the lack of consistent and effective prevention and treatments of PTSD. The American Psychiatric Association suggests a need for more effective pharmacological treatments, especially for veterans with combat-related PTSD. PTSD is very complex and prevention and treatment are urgently needed to sustain Force Health Protection.