Influence of adrenalectomy on the gut microbiome and MDMA-induced hyperthermia.
Amal Aburahma, Srishti Rana, Ray Larsen, Christopher S Ward, Jon E Sprague
European journal of pharmacology April 15, 2023 DOI: 10.1016/j.ejphar.2023.175643 via PubMed
Summary
AI-generated from the abstractMDMA (Ecstasy, Molly, or X) can cause life-threatening hyperthermia. In rats, removing the adrenal glands reduced the temperature increase after MDMA, and giving norepinephrine or corticosterone partially restored it. MDMA also changed the gut microbiome, altering the balance of bacterial groups like Firmicutes, Bacteroidetes, Actinobacteria, Verrucomicrobia, and Proteobacteria. These results indicate a link between the adrenal system, gut bacteria, and MDMA-induced hyperthermia.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Adrenalectomized and sham-operated rats |
| Interventions | MDMA norepinephrine corticosterone |
| Dose | 10 mg/kg MDMA, 3 mg/kg norepinephrine, 3 mg/kg corticosterone |
| Citations | 5 |
| Key finding | MDMA-induced hyperthermia is attenuated in adrenalectomized rats and partially restored by norepinephrine or corticosterone, with concurrent changes in gut microbiome composition. |
Abstract
The increased use of the stimulant drug, 3,4-methylenedioxymethamphetamine (MDMA), more commonly known as Ecstasy, Molly or X, has been linked to the development of life-threatening hyperthermia in human and animal models. The current study aimed to investigate the role of the gut-adrenal axis in MDMA-induced hyperthermia by assessing the influence of the acute exogenous supplementation with norepinephrine (NE) or corticosterone (CORT) to adrenalectomized (ADX) rats following MDMA administration. MDMA (10 mg/kg, sc) resulted in significant increase of body temperature in SHAM animals compared to ADX animals at 30-, 60- and 90-min timepoints post-MDMA treatment. The attenuated MDMA-mediated hyperthermic response seen in ADX animals was partially restored by the exogenous administration of NE (3 mg/kg, ip) or CORT (3 mg/kg, ip) 30 min after MDMA treatment. Additionally, 16 S rRNA analysis revealed distinct changes in the gut microbiome composition and diversity notable by the higher abundance of minor phyla Actinobacteria, Verrucomicrobia and Proteobacteria in ADX rats compared to control and SHAM rats. Furthermore, MDMA administration resulted in marked changes in the dominant phyla Firmicutes and Bacteroidetes and minor phyla Actinobacteria, Verrucomicrobia and Proteobacteria in ADX animals. The most notable changes in the gut microbiome upon CORT treatment were reported with increase in Bacteroidetes and decrease in Firmicutes phyla whereas NE treatment resulted in increase in Firmicutes and decrease in Bacteroidetes and Proteobacteria post treatment. These results suggest a correlation between the sympathoadrenal axis, gut microbiome structure and diversity and MDMA-mediated hyperthermia.