Abstract Title

Methylone: "Ecstasy" by another name

RAD Assignment Number

2105

Presenter Name

Sean Dolan

Abstract

Purpose: Following increased governmental intervention regarding the sale of novel psychoactive substances, the synthetic cathinone derivative methylone has been diverted from “bath salts” into “Ecstasy” formulations in lieu of MDMA; however, it is unknown what effects substitution with methylone may have on “Ecstasy” use. In the current study, we evaluated the pharmacology of methylone in parallel with MDMA using in vitro and in vivo techniques in order to assess its potential for compulsive abuse.

Methods: We assessed the activity of methylone and MDMA at SERT using whole-cell patch clamp electrophysiology. We determined the dopaminergic and serotonergic contributions to the discriminative stimulus effects of both compounds in rats trained to discriminate methamphetamine, DOM, or MDMA from vehicle and utilized the D1-selective antagonist SCH23390 and the 5-HT2A/2C antagonist pirenperone to further probe mechanistic differences. Furthermore, we tested for substitution of methylone and MDMA in rats trained to self-administer methamphetamine under continuous and progressive ratio schedules of reinforcement.

Results: Methylone, like MDMA, produced an inward current at SERT, indicative of an amphetamine-like substrate mechanism. Both methylone and MDMA fully substituted for the discriminative stimulus effects of methamphetamine and MDMA, but only partially for DOM. In methamphetamine-trained rats, SCH2330 fully and dose-dependently attenuated methamphetamine-appropriate responding by methylone and MDMA with similar potencies. SCH23390 and pirenperone both partially attenuated MDMA-appropriate responding by methylone and MDMA, but both antagonists were less efficacious against methylone than MDMA. Methylone and MDMA were both readily self-administered, but there were no significant differences in reinforcing efficacy between the two drugs under either schedule of reinforcement.

Conclusions: These data indicate that methylone possesses similar mechanistic and reinforcing effects as MDMA, and its inclusion in “Ecstasy” formulations is unlikely to produce different subjective effects or increased compulsive use.

Research Area

Pharmacology

Presentation Type

Oral

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Methylone: "Ecstasy" by another name

Purpose: Following increased governmental intervention regarding the sale of novel psychoactive substances, the synthetic cathinone derivative methylone has been diverted from “bath salts” into “Ecstasy” formulations in lieu of MDMA; however, it is unknown what effects substitution with methylone may have on “Ecstasy” use. In the current study, we evaluated the pharmacology of methylone in parallel with MDMA using in vitro and in vivo techniques in order to assess its potential for compulsive abuse.

Methods: We assessed the activity of methylone and MDMA at SERT using whole-cell patch clamp electrophysiology. We determined the dopaminergic and serotonergic contributions to the discriminative stimulus effects of both compounds in rats trained to discriminate methamphetamine, DOM, or MDMA from vehicle and utilized the D1-selective antagonist SCH23390 and the 5-HT2A/2C antagonist pirenperone to further probe mechanistic differences. Furthermore, we tested for substitution of methylone and MDMA in rats trained to self-administer methamphetamine under continuous and progressive ratio schedules of reinforcement.

Results: Methylone, like MDMA, produced an inward current at SERT, indicative of an amphetamine-like substrate mechanism. Both methylone and MDMA fully substituted for the discriminative stimulus effects of methamphetamine and MDMA, but only partially for DOM. In methamphetamine-trained rats, SCH2330 fully and dose-dependently attenuated methamphetamine-appropriate responding by methylone and MDMA with similar potencies. SCH23390 and pirenperone both partially attenuated MDMA-appropriate responding by methylone and MDMA, but both antagonists were less efficacious against methylone than MDMA. Methylone and MDMA were both readily self-administered, but there were no significant differences in reinforcing efficacy between the two drugs under either schedule of reinforcement.

Conclusions: These data indicate that methylone possesses similar mechanistic and reinforcing effects as MDMA, and its inclusion in “Ecstasy” formulations is unlikely to produce different subjective effects or increased compulsive use.