Reversal of temperature responses to methylone mediated through bi-directional fecal microbiota transplantation between hyperthermic tolerant and naïve rats

Goldsmith, Robert S.; Aburahma, Amal; Pachhain, Sudhan; Choudhury, Sayantan Roy; Phuntumart, Vipa; Larsen, Ray A.; Ward, Christopher; Sprague, Jon E.

doi:10.1080/23328940.2022.2069965

Cited by 6 publications

(3 citation statements)

References 48 publications

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“…One other potential limitation here is the fact that repeated exposures to eutylone over conditioning may have impacted its aversive and/or rewarding effects as a function of tolerance/sensitization. In this context, it is interesting to note that in other preparations tolerance and sensitization to synthetic cathinones have been reported following repeated exposures (see Goldsmith et al, 2019Goldsmith et al, , 2022Lo ´pez-Arnau et al, 2017). Determining the contribution of tolerance/sensitization to taste and place conditioning is a potentially important issue regarding the relative strength of these effects in acute and chronic designs (see Siegel et al, 1995, for a discussion).…”

Section: Study Limitationsmentioning

confidence: 99%

Conditioned taste avoidance and conditioned place preference induced by the third-generation synthetic cathinone eutylone in female sprague-dawley rats.

Jones¹,

Huang²,

Manke³

et al. 2023

Experimental and Clinical Psychopharmacology

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Recently, use of the synthetic cathinone (aka "bath salt") eutylone has risen in the United States and globally. Due to its novelty in drug markets, its affective properties remain largely uninvestigated. In this context, drugs of abuse have both rewarding and aversive effects and understanding these effects, their relative balance, and factors that impact each are important to understanding the likelihood of drug use and abuse. This investigation attempted to characterize eutylone's rewarding and aversive effects in a combined conditioned taste avoidance/place preference assay. Female Sprague-Dawley rats were given 20-min access to saccharin, injected with one of five doses of eutylone (0, 3, 10, 18, 32 mg/kg; intraperitoneally; IP), and placed on one side of a place conditioning apparatus. On the following day, subjects were given 20-min access to water, injected IP with vehicle, and placed on the other side of the apparatus. After five conditioning cycles, place preference and saccharin avoidance were assessed. Eutylone induced significant taste avoidance but did not significantly increase time spent on the drug-paired side (relative to controls). Excluding animals with high initial side preference, however, eutylone induced a preference at all doses with the high dose group displaying higher preference than controls. There was no significant correlation between eutylone's aversive and rewarding effects. These data indicate that eutylone (like other synthetic cathinones) induces both rewarding and aversive effects and highlight the need to assess the impact of various factors on its affective properties (and their balance) and on their use and abuse. Public Health SignificanceThis study is the first to demonstrate taste avoidance and place preference induced by the novel synthetic cathinone eutylone. Given that a drug's aversive and rewarding effects are thought in balance to mediate its use and abuse, the present study indicates the potential abuse of eutylone and the importance in assessing various factors that could affect this liability.

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Section: Study Limitationsmentioning

confidence: 99%

Conditioned taste avoidance and conditioned place preference induced by the third-generation synthetic cathinone eutylone in female sprague-dawley rats.

Jones¹,

Huang²,

Manke³

et al. 2023

Experimental and Clinical Psychopharmacology

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“…Additionally, NE also prevents heat dissipation through α 1 -adrenergic receptor mediated vasoconstriction 4 . Recently, the roles of non-host contributors, particularly the gut microbiome, have been recognized for their influence on PIH 5 , 6 . Application of gut bacterial modulation methods such as antibiotic treatment 5 and fecal microbial transplantation (FMT) 6 showed that gut bacteria are likely playing a contributing role in PIH.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, the roles of non-host contributors, particularly the gut microbiome, have been recognized for their influence on PIH 5 , 6 . Application of gut bacterial modulation methods such as antibiotic treatment 5 and fecal microbial transplantation (FMT) 6 showed that gut bacteria are likely playing a contributing role in PIH. However, the specific mechanism(s) by which the gut microbiome could affect PIH has not been elucidated.…”

Section: Introductionmentioning

confidence: 99%

Bile acids and the gut microbiome are involved in the hyperthermia mediated by 3,4-methylenedioxymethamphetamine (MDMA)

Rana,

Canfield,

Ward

et al. 2024

Sci Rep

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Hyperthermia induced by phenethylamines, such as 3,4–methylenedioxymethamphetamine (MDMA), can lead to life-threatening complications and death. Activation of the sympathetic nervous system and subsequent release of norepinephrine and activation of uncoupling proteins have been demonstrated to be the key mediators of phenethylamine-induced hyperthermia (PIH). Recently, the gut microbiome was shown to also play a contributing role in PIH. Here, the hypothesis that bile acids (BAs) produced by the gut microbiome are essential to PIH was tested. Changes in the serum concentrations of unconjugated primary BAs cholic acid (CA) and chenodeoxycholic acid (CDCA) and secondary BA deoxycholic acid (DCA) were measured following MDMA (20 mg/kg, sc) treatment in antibiotic treated and control rats. MDMA-induced a significant hyperthermic response and reduced the serum concentrations of three BAs 60 min post-treatment. Pretreatment with antibiotics (vancomycin, bacitracin and neomycin) in the drinking water for five days resulted in the depletion of BAs and a hypothermic response to MDMA. Gut bacterial communities in the antibiotic-treated group were distinct from the MDMA or saline treatment groups, with decreased microbiome diversity and alteration in taxa. Metagenomic functions inferred using the bioinformatic tool PICRUSt2 on 16S rRNA gene sequences indicated that bacterial genes associated to BA metabolism are less abundant in the antibiotic-MDMA treated group. Overall, these findings suggest that gut bacterial produced BAs might play an important role in MDMA-induced hyperthermia.

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The pharmacology and neurotoxicology of synthetic cathinones

Angoa-Perez,

Kuhn

2024

Advances in Pharmacology

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Reversal of temperature responses to methylone mediated through bi-directional fecal microbiota transplantation between hyperthermic tolerant and naïve rats

Cited by 6 publications

References 48 publications

Conditioned taste avoidance and conditioned place preference induced by the third-generation synthetic cathinone eutylone in female sprague-dawley rats.

Conditioned taste avoidance and conditioned place preference induced by the third-generation synthetic cathinone eutylone in female sprague-dawley rats.

Bile acids and the gut microbiome are involved in the hyperthermia mediated by 3,4-methylenedioxymethamphetamine (MDMA)

The pharmacology and neurotoxicology of synthetic cathinones

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