Acute Effects of 3,4-Methylenedioxymethamphetamine (MDMA) and R(-) MDMA on Actigraphy-Based Daytime Activity and Sleep Parameters in Rhesus Monkeys

• Type of Material: Article
• Authors: Lais F. Berro, Emory University; Hannah Shields, Emory University; Melis Odabas-Geldiay, Emory University; Barbara O Rothbaum, Emory University; Monica L. Andersen, Emory University; Leonard Howell, Emory University
• Language: English
• Date: 2018-08-01
• Publisher: American Psychological Association
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 American Psychological Association.
• Final Published Version (URL): http://dx.doi.org/10.1037/pha0000196
• Title of Journal or Parent Work: Experimental and Clinical Psychopharmacology
• ISSN: 1064-1297
• Volume: 26
• Issue: 4
• Start Page: 410
• End Page: 420
• Grant/Funding Information: This research was supported by USPHS Grants DA10344 (LLH), DA031246 (LLH) and ODP51OD11132 (Yerkes); AFIP and FAPESP Grant 2015/25482-3 (LFB).
• Keywords: rhesus monkeys; SEROTONIN TRANSPORTERS; sleep; NONHUMAN-PRIMATES; 3,4-methylenedioxymethamphetamine; Psychiatry; Pharmacology & Pharmacy; Social Sciences; METHAMPHETAMINE; (+/-)3,4-METHYLENEDIOXYMETHAMPHETAMINE; Psychology, Clinical; ECSTASY USERS; Science & Technology; TEMPERATURE; Psychology; NEUROTOXICITY; MEMORY; actigraphy; stereoisomer; POSTTRAUMATIC-STRESS-DISORDER; Life Sciences & Biomedicine; Psychology, Biological; DOPAMINE
• Research Categories: Biology, Neuroscience; Psychology, Psychobiology; Psychology, Behavioral

Abstract

3,4-Methylenedioxymethamphetamine (MDMA) affects monoaminergic pathways that play a critical role in sleep-wake cycles. Dopaminergic mechanisms are thought to mediate the sleep-disrupting effects of stimulant drugs. However, the mechanisms underlying the effects of MDMA on sleep-wake cycles and the effects of R(-) MDMA, a stereoisomer that lacks dopaminergic activity, on sleep remain unknown. The aim of the present study was to investigate the effects of racemic MDMA and R(-) MDMA on daytime activity and sleep-like parameters evaluated with actigraphy in adult rhesus macaques (Macaca mulatta, n = 6). Actiwatch monitors were attached to the monkeys' collars and actigraphy recording was conducted during baseline conditions and after the administration of acute intramuscular injections of saline (vehicle), racemic MDMA (0.3, 1.0, or 1.7 mg/kg), or R(-) MDMA (0.3, 1.0, or 1.7 mg/kg) at 9 or 16 h (3 h before "lights off"). Morning treatments had no effects on sleep-like parameters. Racemic MDMA decreased general daytime activity during the first hour after injection and increased daytime activity at 3 hr posttreatment. Although afternoon administration of racemic MDMA increased sleep latency, it improved other sleep parameters, decreasing wake time after sleep onset (WASO) and increasing sleep efficiency for subjects with low baseline sleep efficiency. Afternoon treatment with R(-) MDMA improved sleep measures, increasing sleep efficiency and decreasing sleep latency and WASO, while having no effects on daytime activity. The stimulant and sleep-disrupting effects of racemic MDMA are likely mediated by dopaminergic and noradrenergic mechanisms, while serotonergic pathways appear to be involved in the sleep-promoting effects of MDMA.