±3,4-METHYLENEDIOXYMETHAMPHETAMINE ADMINISTRATION ALTERS HEROIN WITHDRAWAL-ENHANCED FEAR LEARNING AND ATTENUATES DORSAL HIPPOCAMPAL INTERLEUKIN-1β, TUMOR NECROSIS FACTOR-α, AND GLIAL FIBRILLARY ACIDIC PROTEIN

This study investigated the effects of MDMA on heroin withdrawal-enhanced fear learning (HW-EFL), a preclinical model of comorbid OUD and PTSD. Animals underwent 10 days of chronic escalating doses of heroin and were subsequently administered MDMA or saline during heroin withdrawal. One week after the start of heroin withdrawal, animals were exposed to a mild foot shock in a distinct environment and tested subsequently for enhanced fear learning. We found MDMA weakened the heroin withdrawal-induced enhancement of future fear learning. To investigate the mechanism underlying this effect, we examined changes in IL-1β, TNF-α, and GFAP within the DG of the DH in a separate cohort of animals that received MDMA or saline during heroin withdrawal. We found MDMA administration attenuated heroin withdrawal-induced increases in IL-1β, TNF-α, and GFAP in the DG of the DH, suggesting that the effect of MDMA during HW-EFL is partly due to a neuroimmune mechanism.