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Differential sensitivity to detect prosocial effects of 3,4-methylenedioxymethamphetamine (MDMA) in different social approach paradigms in mice.

ABSTRACT: A recreational drug, 3,4-methylenedioxymethamphetamine (MDMA), has prosocial effects including increased sociability, enhancement of trust feelings, and empathy. Although several methods, such as the social interaction and three chamber tests, have been used, the neural mechanisms underlying the prosocial effects have not been well understood. In the present study, based on a social approach paradigm using a single-chamber apparatus, we have developed two reproducible and simple social approach tests, SAT1 and SAT2, in ICR mice. In the SAT1, an unfamiliar mouse was set in a wire mesh cylinder cage that was placed in the center of a rectangular open field, while in the SAT2, an unfamiliar mouse was set in a wire mesh rectangular cage that was placed along a wall of a rectangular open field. Although MDMA treatment enhanced sociability in both SAT1 and SAT2, the ratio of high sociability mice was higher in the SAT2 than in the SAT1, indicating a differential sensitivity to detect the prosocial effects. Thus, we suggest that the SAT2 is a promising and suitable method to explore the neuronal mechanisms underlying the effects of MDMA.

SUBMITTER: Mukai S

PROVIDER: S-EPMC7722663 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Differential sensitivity to detect prosocial effects of 3,4-methylenedioxymethamphetamine (MDMA) in different social approach paradigms in mice.

Mukai Satoko S Nakada Sao S Kamada Hikari H Yaguchi Ryuma R Deyama Satoshi S Kaneda Katsuyuki K

Neuropsychopharmacology reports 20200630 3

A recreational drug, 3,4-methylenedioxymethamphetamine (MDMA), has prosocial effects including increased sociability, enhancement of trust feelings, and empathy. Although several methods, such as the social interaction and three chamber tests, have been used, the neural mechanisms underlying the prosocial effects have not been well understood. In the present study, based on a social approach paradigm using a single-chamber apparatus, we have developed two reproducible and simple social approach ...[more]

PMID: 32608059

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Project description:3,4-Methylenedioxymethamphetamine (MDMA) is an illicit phenethylamine ingested for entactogenic and euphoric effects. Although blood is more commonly submitted for forensic analysis, previous human MDMA pharmacokinetics research focused on plasma data; no direct blood-plasma comparisons were drawn. Blood and plasma specimens from 50 healthy adult volunteers (33 males, 17 females, 36 African-American) who ingested recreational 1.0 and 1.6 mg/kg MDMA doses were quantified for MDMA and metabolites 4-hydroxy-3-methoxymethamphetamine (HMMA), 3,4-methylenedioxyamphetamine (MDA), and 4-hydroxy-3-methoxyamphetamine (HMA) by two-dimensional gas chromatography-mass spectrometry. Specimens were collected up to 3 h post-dose and evaluated for maximum concentration (C max), first detection time (t first), time of C max (t max), and 3-h area under the curve (AUC0-3 h); as well as blood metabolite ratios and blood/plasma ratios. Median blood MDMA and MDA C max were significantly greater (p?<?0.0005) than in plasma, but HMMA was significantly less (p?<?0.0005). HMA was detected in few blood specimens, at low concentrations. Nonlinear pharmacokinetics were not observed for MDMA or MDA in this absorptive phase, but HMMA C max and AUC0-3 h were similar for both doses despite the 1.6-fold dose difference. Blood MDA/MDMA and MDA/HMMA significantly increased (p?<?0.0001) over the 3-h time course, and HMMA/MDMA significantly decreased (p?<?0.0001). Blood MDMA C max was significantly greater in females (p?=?0.010) after the low dose only. Low-dose HMMA AUC0-3 h was significantly decreased in females' blood and plasma (p?=?0.027) and in African-Americans' plasma (p?=?0.035). These data provide valuable insight into MDMA blood-plasma relationships for forensic interpretation and evidence of sex- and race-based differential metabolism and risk profiles. Figure Median (interquartile range) blood/plasma 3,4-methylenedioxymethamphetamine (MDMA) (a), 4-hydroxy-3-methoxymethamphetamine (HMMA) (b), and 3,4-methylenedioxyamphetamine (MDA) (c) ratios for 3 h after controlled MDMA administration. Changes over time were significant after the 1.6 mg/kg dose for HMMA and MDA (p?=?0.013 and p?=?0.021), but not for MDMA. No changes over time were significant after the 1.0 mg/kg dose. Note: y-axes do not begin at 0. *p ?<?0.05 (low vs. high).

Dataset Information

Differential sensitivity to detect prosocial effects of 3,4-methylenedioxymethamphetamine (MDMA) in different social approach paradigms in mice.

Publications

Differential sensitivity to detect prosocial effects of 3,4-methylenedioxymethamphetamine (MDMA) in different social approach paradigms in mice.

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