Influence of adrenalectomy on the gut microbiome and MDMA-induced hyperthermia.

Amal Aburahma; Srishti Rana; Ray A. Larsen; Christopher S Ward; Jon E. Sprague

doi:10.1016/j.ejphar.2023.175643

Influence of adrenalectomy on the gut microbiome and MDMA-induced hyperthermia.

Amal Aburahma, Srishti Rana, Ray A. Larsen, Christopher S Ward, Jon E. Sprague

European Journal of Pharmacology April 15, 2023 DOI: 10.1016/j.ejphar.2023.175643 (opens in new tab)

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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
Topics	MDMA
Citations	5
Key findings	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.

Comparable studies

Other preclinical and animal studies on MDMA, most cited first.

Study	Year	Design
Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context)	1987	Experimental study
3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain	1987	Animal experiment
Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells	2006	In vitro laboratory study
Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Rats	1998	Experimental study
Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery Squirrel monkeys treated with MDMA	1999	Observational cohort

Citations in the library

Cited by 4

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