Post-traumatic stress disorder (
PTSD) is a devastating disorder that involves maladaptive changes in immune status. Using the stress-enhanced fear learning (SEFL) paradigm, an animal model of
PTSD, our laboratory has demonstrated increased pro-inflammatory
cytokine immunoreactivity in the hippocampus following severe stress. Recent clinical trials have demonstrated 3,4-methylenedioxymethamphetamine (
MDMA)-assisted psychotherapy as an effective novel treatment for
PTSD. Interestingly,
MDMA has been shown to have an immunosuppressive effect in both pre-clinical and clinical studies. Therefore, we predict
MDMA administration may attenuate SEFL, in part, due to an immunosuppressive mechanism. The current studies test the hypothesis that
MDMA is capable of attenuating SEFL and inducing alterations in expression of TNF-α, IL-1β,
glial fibrillary acidic protein (GFAP), an astrocyte specific marker, and ionized
calcium-binding adapter molecule -1 (IBA-1), a microglial specific marker, in the dorsal hippocampus (DH) following a severe stressor in male animals. To this end, experiment 1 determined the effect of
MDMA administration 0, 24, and 48 h following a severe foot
shock stressor on SEFL. We identified that
MDMA administration significantly attenuated SEFL. Subsequently, experiment 2 determined the effect of
MDMA administration following a severe stressor on the expression of TNF-α, IL-1β, GFAP, and IBA-1 in the DH. We found that
MDMA administration significantly attenuated stress-induced IL-1β and stress-reduced IBA-1 but had no effect on TNF-α or GFAP. Overall, these results support the hypothesis that
MDMA blocks SEFL through an immunosuppressive mechanism and supports the use of
MDMA as a potential therapeutic agent for those experiencing this disorder. Together, these experiments are the first to examine the effect of
MDMA in the SEFL model and these data contribute significantly towards the clinical
PTSD findings.