Hyperthermia is one of the most acute and life-threatening consequences of 3,4-methylenedioxymethamphetamine (MDMA) use. The hyperthermia induced by MDMA involves a complex interaction between heat generation and loss of heat dissipation. Recent studies have demonstrated a role for gut microbiome in the regulation of body weight and temperature. Here, we investigated the potential role of the gut microbiome in MDMA-mediated hyperthermia. For fourteen days prior to treatment with MDMA (20 mg/kg, sc) male, Sprague-Dawley rats were provided regular drinking water or drinking water laced with the non-absorbable antibiotics, bacitracin (0.5 mg/mL), neomycin (2mg/mL), and vancomycin (0.2mg/mL). Antibiotic (ABX) treatment reduced gut bacteria and increased cecal size. MDMA-induced a hyperthermic response that resulted in a maximal temperature change (ΔTmax ) of 4.6 ± 0.1 °C and only a 50% survival rate 60 minutes after treatment. Conversely, ABX treatment prior to MDMA attenuated the hyperthermic response with a ΔTmax of 3.4 ± 0.6 °C and a 100% survival rate 60 minutes after treatment. An acute intraperitoneal injection of ABX 30 minutes before MDMA had no effect on the hyperthermic response, eliminating the possibility of a pharmacodynamics interaction between ABX and MDMA. Overall, these findings demonstrate that the gut microbiome contributes to the hyperthermia mediated by MDMA.
Dr. Jon Sprague
First Advisor Department
Dr. Vipaporn Phuntumart
Second Advisor Department
Ridge, Emily, "Host Microbiome Regulation of Hyperthermia Mediated by 3,4-Methylenedioxymethamphetamine (MDMA, Molly)" (2017). Honors Projects. 681.