MDMA and memory, addiction, and depression: dose-effect analysis

作者：Madeline M. Pantoni, Jinah L. Kim, Kaitlin R. Van Alstyne, Stephan Anagnostaras · 发表于：Psychopharmacology · 年份：2022 · DOI：10.1007/s00213-022-06086-9 · 被引用次数：34 · 研究领域：Psychedelics and Drug Studies、Forensic Toxicology and Drug Analysis、Cannabis and Cannabinoid Research

RATIONALE: ±3,4-Methylenedioxymethamphetamine (MDMA) is a recreational drug that shows substantial promise as a psychotherapeutic agent. Still, there is some concern regarding its behavioral toxicity, and its dose-effect relationship is poorly understood. We previously explored the role of dose in the cognitive effects of MDMA in a systematic review of existing literature and found no evidence in animals that MDMA impairs memory at low doses (< 3 mg/kg) but mixed results at high doses (≥ 3 mg/kg). Since this review comprised mostly of single-dose studies and an assortment of methodologies, an empirical dose-ranging study on this topic is warranted. OBJECTIVES: The current study aims to evaluate the conclusion from our systematic review that 3 mg/kg may be the threshold for MDMA-induced amnesia, and to further understand the dose-effect relationship of MDMA on behavioral assays of memory, addiction, and depression. METHODS: We systematically examined the effects of 0.01 to 10 mg/kg MDMA on Pavlovian fear conditioning; behavioral sensitization, conditioned place preference, and conditioned responding; and the Porsolt forced swim test in mice. RESULTS: High doses of MDMA (≥ 3 mg/kg) produced amnesia of fear conditioning memory, some evidence of an addictive potential, and antidepressant effects, while low doses of MDMA (≤ 1 mg/kg) had no effect on these behaviors. CONCLUSIONS: The present dose-ranging study provides further evidence that 3 mg/kg is the threshold for MDMA-induced...