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0159 Acute Effects of 3,4-methylenedioxymethamphetamine (MDMA) And R(−)MDMA on Actigraphy-based Daytime Activity and Sleep Parameters in Rhesus Monkeys
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0159 Acute Effects of 3,4-methylenedioxymethamphetamine (MDMA) And R(−)MDMA on Actigraphy-based Daytime Activity and Sleep Parameters in Rhesus Monkeys
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0159 Acute Effects of 3,4-methylenedioxymethamphetamine (MDMA) And R(−)MDMA on Actigraphy-based Daytime Activity and Sleep Parameters in Rhesus Monkeys
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Journal Article
0159 Acute Effects of 3,4-methylenedioxymethamphetamine (MDMA) And R(−)MDMA on Actigraphy-based Daytime Activity and Sleep Parameters in Rhesus Monkeys
2018
Overview
Abstract
Introduction
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.
Methods
Actiwatch monitors were attached to the monkeys’ collars (Macaca mulatta, n = 6) 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 9h or 16h (3h prior to “lights off”).
Results
Morning treatments had no effects on sleep-like parameters. Racemic MDMA decreased general daytime activity during the 1st hour after injection and increased daytime activity at 3 hours post-treatment. Although afternoon administration of racemic MDMA increased sleep latency for all subjects, it improved other sleep parameters for subjects with poor baseline sleep, decreasing wake time after sleep onset (WASO) and increasing sleep efficiency. Afternoon treatment with R(−) MDMA improved sleep measures for all subjects, increasing sleep efficiency and decreasing sleep latency and WASO, while having no effects on daytime activity.
Conclusion
Our findings suggest that the stimulant and sleep-disrupting (increase in sleep latency) effects of racemic MDMA are likely mediated by dopaminergic mechanisms, while serotonergic pathways appear to be involved in the sleep-promoting effects of MDMA.
Support (If Any)
USPHS grants DA010344 (LLH), DA031246 (LLH), and ODP51OD11132 (Yerkes), AFIP, FAPESP grants 2015/16109-7 (LFB) and 2015/25482–3 (LFB), UMMC Institutional Funds (LFB).
