The widespread use of the stimulant drug 3,4-methylenedioxymethamphetamine (MDMA), commonly referred to as Ecstasy, Molly, or X, has been associated with life-threatening hyperthermia in both humans and animal models. This study aimed to explore the role of the gut-adrenal axis in MDMA-induced hyperthermia by examining the effects of acute exogenous supplementation with norepinephrine (NE) or corticosterone (CORT) in adrenalectomized (ADX) rats following MDMA administration. MDMA (10 mg/kg, subcutaneous) significantly elevated body temperature in SHAM animals compared to ADX animals at 30-, 60-, and 90-minute intervals post-treatment. The attenuated hyperthermic response observed in ADX animals was partially restored with exogenous administration of NE (3 mg/kg, intraperitoneal) or CORT (3 mg/kg, intraperitoneal) 30 minutes after MDMA treatment. Additionally, 16S rRNA analysis revealed notable differences in gut microbiome composition and diversity, including a higher abundance of minor phyla Actinobacteria, Verrucomicrobia, and Proteobacteria in ADX rats compared to control andSHAM rats. MDMA administration further induced significant changes in the dominant phyla Firmicutes and Bacteroidetes, as well as minor phyla Actinobacteria, Verrucomicrobia, and Proteobacteria in ADX animals. Exogenous CORT treatment increased Bacteroidetes and decreased Firmicutes, while NE treatment increased Firmicutes and decreased Bacteroidetes and Proteobacteria. These findings highlight a potential relationship between the sympathoadrenal axis, gut microbiome composition, and MDMA-induced hyperthermia
The widespread use of the stimulant drug 3,4-methylenedioxymethamphetamine (MDMA), commonly referred to as Ecstasy, Molly, or X, has been associated with life-threatening hyperthermia in both humans and animal models. This study aimed to explore the role of the gut-adrenal axis in MDMA-induced hyperthermia by examining the effects of acute exogenous supplementation with norepinephrine (NE) or corticosterone (CORT) in adrenalectomized (ADX) rats following MDMA administration. MDMA (10 mg/kg, subcutaneous) significantly elevated body temperature in SHAM animals compared to ADX animals at 30-, 60-, and 90-minute intervals post-treatment. The attenuated hyperthermic response observed in ADX animals was partially restored with exogenous administration of NE (3 mg/kg, intraperitoneal) or CORT (3 mg/kg, intraperitoneal) 30 minutes after MDMA treatment. Additionally, 16S rRNA analysis revealed notable differences in gut microbiome composition and diversity, including a higher abundance of minor phyla Actinobacteria, Verrucomicrobia, and Proteobacteria in ADX rats compared to control andSHAM rats. MDMA administration further induced significant changes in the dominant phyla Firmicutes and Bacteroidetes, as well as minor phyla Actinobacteria, Verrucomicrobia, and Proteobacteria in ADX animals. Exogenous CORT treatment increased Bacteroidetes and decreased Firmicutes, while NE treatment increased Firmicutes and decreased Bacteroidetes and Proteobacteria. These findings highlight a potential relationship between the sympathoadrenal axis, gut microbiome composition, and MDMA-induced hyperthermia
№ | Муаллифнинг исми | Лавозими | Ташкилот номи |
---|---|---|---|
1 | Usanova S.T. | Senior lecturer | Alfraganus university |
№ | Ҳавола номи |
---|---|
1 | 1.A. Aburahma, S. Pachhain, S.R. Choudhury, S. Rana, V. Phuntumart, R. Larsen, J.E. Sprague.Potential contribution of the intestinal microbiome to phenthylamine-induced hyperthermia.Brain Behav. Evol., 95 (2020), pp. 256-271. https://doi.org/10.1159/0005120982.M. Angoa-Pérez, B. Zagorac, A.D. Winters, J.M. Greenberg, M. Ahmad, K.R. Theis, D.M. Kuhn.Differential effects of synthetic psychoactive cathinones and amphetamine stimulants on the gut microbiome in mice.PLoS One, 15 (2020), Article e0227774. https://doi.org/10.1371/journal.pone.02277743.M. Angoa-Pérez, B. Zagorac, D.M. Francescutti, K.R. Theis, D.M. Kuhn.Responses to chronic corticosterone on brain glucocorticoid receptors, adrenal gland, and gut microbiota in mice lacking neuronal serotonin.Brain Res., 1751 (2021), Article 147190. https://doi.org/10.1016/j.brainres.2020.1471904.M.T. Bailey, J.W. Karaszewski, G.R. Lubach, C.L. Coe, M. Lyte.In vivo adaptation of attenuated Salmonella typhimuriumresults in increased growth upon exposure to norepinephrine.Physiol. Behav., 67 (1999), pp. 359-364. https://doi.org/10.1016/S0031-9384(99)00087-65.B.J. Callahan, P.J. McMurdie, M.J. Rosen, A.W. Han, A.J.A. Johnson, S.P. Holmes.DADA2: high-resolution sample inference from Illumina amplicon data.Nat. Methods, 13 (2016), pp. 581-583. https://doi.org/10.1038/nmeth.38696.M.I. Colado, J.L. Williams, A.R. Green.The hyperthermic and neurotoxic effects of “Ecstasy” (MDMA) and 3,4 methylenedioxyamphetamine (MDA) in the Dark Agouti (DA) rat, a model of the CYP2D6 poor metabolizer phenotype.Br. J. Pharmacol., 115 (1995), pp. 1281-1289.7.M. Crumeyrolle-Arias, M. Jaglin, A. Bruneau, S. Vancassel, A. Cardona, V. Daugé, L. Naudon, S. Rabot.Absence of the gut microbiota enhances anxiety-like behavior and neuroendocrine response to acute stress in rats.Psychoneuroendocrinology, 42 (2014), pp. 207-217. https://doi.org/10.1016/j.psyneuen.2014.01.0148.R.I. Dafters.Hyperthermia following MDMA administration in rats: effects of ambient temperature, water consumption, and chronic dosing.Physiol. Behav., 58(1995), pp. 877-882. https://doi.org/10.1016/0031-9384(95)00136-79.L. Desbonnet, G. Clarke, A. Traplin, O. O'Sullivan, F. Crispie, R.D. Moloney, P.D. Cotter, T.G. Dinan, J.F. Cryan.Gut microbiota depletion from early adolescence in mice: implications for brain and behaviour.Brain Behav. Immun., 48 (2015), pp. 165-173. https://doi.org/10.1016/j.bbi.2015.04.00410.L.A. Downey, H. Sands, L. Jones, A. Clow, P. Evans, T. Stalder, A.C. Parrott.Reduced memory skills and increased hair cortisol levels in recent Ecstasy/MDMA users: significant but independent neurocognitive and neurohormonal deficits.Hum. Psychopharmacol. Clin. Exp.,30 (2015), pp. 199-207. https://doi.org/10.1002/hup.247411.F. Fernandez, S. Aguerre, P. Mormède, F. Chaouloff.Influences of the corticotropic axis and sympathetic activity on neurochemical consequences of 3,4-methylenedioxymethamphetamine (MDMA) administration in Fischer 344 rats.Eur. J. Neurosci., 16 (2002), pp. 607-618. https://doi.org/10.1046/j.1460-9568.2002.02110.x12.J.M. García-Montes, M. Pérez-Álvarez, M.Á. Sánchez-Moya, J.A.C. Torres, D.F. Carreno, S.P. Garcelán, L. del C. Sánchez-Sánchez.Ecstasy (MDMA): a rebellion coherent with the system.Nordic Stud. Alcohol Drugs, 38 (2021), pp. 89-102.https://doi.org/10.1177/145507252095432913.R. Goldsmith, A. Aburahma, S. Pachhain, S.R. Choudhury, V. Phuntumart, R. Larsen, C.S. Ward, J.E. Sprague.Reversal of temperature responses to methylone mediated through bi-directional fecal microbiota transplantation between hyperthermic tolerant and naïve rats.Temperature, 9 (2022), pp. 318-330. https://doi.org/10.1080/23328940.2022.206996514.N.R. Herring, G.A. Gudelsky, C.V. Vorhees, M.T. Williams.(+)-Methamphetamine-induced monoamine reductions and impaired egocentric learning in adrenalectomized rats is independent of hyperthermia.Synapse, 64 (2010), pp. 773-785. https://doi.org/10.1002/syn.2078415.C.M. Hysek, A.E. Fink, L.D. Simmler, M. Donzelli, E. Grouzmann, M.E. Liechti.Alpha-adrenergic receptors contribute to the acute effects of MDMA in humans.J. Clin. Psychopharmacol., 33 (2013), pp. 658-666. https://doi.org/10.1097/JCP.0b013e3182979d3216.C.M. Hysek, Y. Schmid, A. Rickli, M.E. Liechti.Carvedilol inhibits the cardiostimulant and thermogenic effects of MDMA in humans: lost in translation.Br. J. Pharmacol., 170 (2013), pp. 1273-1275. https://doi.org/10.1111/bph.1239817.Q.F. Liu, H.-M. Kim, S. Lim, M.-J. Chung, C.-Y. Lim, B.-S. Koo, S.-S. Kang.Effect of probiotic administration ongut microbiota and depressive behaviors in mice.DARU J. Pharm. Sci., 28 (2020), pp. 181-189. https://doi.org/10.1007/s40199-020-00329-w18.M. Lyte, B.P. Arulanandam, C.D. Frank.Production of Shiga-like toxins by Escherichia coliO157:H7 can be influenced by the neuroendocrine hormone norepinephrine.J. Lab. Clin. Med., 128 (1996), pp. 392-398. https://doi.org/10.1016/s0022-2143(96)80011-419.M. Lyte, M.T. Bailey.Neuroendocrine-bacterial interactions in a neurotoxin-induced model of trauma.J. Surg. Res., 70 (1997), pp. 195-201. https://doi.org/10.1006/jsre.1997.513020.T. Makisumi, K. Yoshida, T. Watanabe, N. Tan, N. Murakami, A. Morimoto.Sympatho-adrenal involvement in methamphetamine-induced hyperthermia through skeletal muscle hypermetabolism.Eur. J. Pharmacol., 363 (1998),pp. 107-112. https://doi.org/10.1016/S0014-2999(98)00758-4 |