The temporal dynamics of the effects of monoacylglycerol lipase blockade on locomotion, anxiety, and body temperature
Abstract
Studies with the monoacylglycerol lipase blocker JZL184 have suggested that enhanced 2-arachidonoylglycerol signaling suppresses locomotion, lowers body temperature, and decreases anxiety. Although the neurochemical effects of JZL184 develop within 30 min, its behavioral and autonomic effects have been studied much later. To clarify temporal dynamics, we studied the effects of intraperitoneal injections of JZL184 in mice on home-cage locomotion and body temperature for 120 min using in-vivo biotelemetry. We also studied the effects of 4, 8, and 16 mg/kg JZL184 in the open field and elevated plus maze at various time points. In the home cage, JZL184 blunted injection-induced body temperature increases but exerted no long-term effects. Vehicle injections increased the duration of rapid movements whereas the duration of motionless periods was decreased, a pattern also abolished by JZL184. Although the highest dose exerted a mild long-term effect on the relative duration of motionless periods, JZL184 seemed to have phasic rather than tonic effects in the home cage. By contrast, open field and plus maze behavior was affected 80 and 120 min but not 40 min after treatments, which may indicate tonic rather than phasic effects in these tests. Our findings confirm earlier reports of a mild anxiolytic effect of JZL184, but surprisingly, the compound markedly and dose dependently increased locomotion in the open field in both CD1 and C57BL/6J mice. These findings are difficult to reconcile at present, but suggest that the effects of monoacylglycerol lipase inhibition are more complex than previously believed and may depend strongly on as yet unidentified factors such as environmental conditions, the time of testing, species/strains, etc.
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Augmentation of 2-AG signaling through MAGL inhibition produces anxiolytic-like effects that are particularly prominent or entirely restricted to conditions of high environmental aversiveness.
“augmentation of 2-AG signaling through MAGL inhibition produces anxiolytic-like effects that, similar to the effects of FAAH inhibitors, are particularly prominent or entirely restricted to conditions of high environmental aversiveness – possibly reflecting the on-demand synthesis of 2-AG that is augmented by exposure to stress (Aliczki et al., 2012; Aliczki et al., 2013; Busquets-Garcia et al., 2”
From The endocannabinoid system as a target for novel anxiolytic drugs (2017) · cites this paper as Aliczki et al., 2012
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- Authors
- Aliczki, M., Balogh, Z., Tulogdi, A., & Haller, J.
- Venue
- Behavioural Pharmacology
- Published
- 2012-08
- Volume
- 23
- Issue
- 4
- Pages
- 348-357
- ISSN
- 0955-8810 (ISSN-L)
- OpenAlex
- W2083191903
- Cited by
- 37
- References
- 0
- Citations by year
- 2025: 3 · 2024: 1 · 2022: 2 · 2021: 4 · 2020: 1 · 2019: 1 · 2018: 5 · 2017: 3 · 2016: 2 · 2015: 5 · 2014: 3 · 2013: 6 · 2012: 1
- FWCI
- 3.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioural Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Hungarian Scientific Research Fund
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- monoacylglycerol lipase inhibition, JZL184, 2-arachidonoylglycerol, endocannabinoid system, locomotion, anxiety, body temperature, temporal dynamics, home cage behavior, elevated plus maze, open field, dose dependence, strain differences
- MeSH terms
- Animals, Anxiety, Behavior, Animal, Body Temperature, Dose-Response Relationship, Drug, Injections, Intraperitoneal, Locomotion, Male, Mice, Inbred C57BL, Monoacylglycerol Lipases, Piperidines, Time Factors, Anti-Anxiety Agents, Maze Learning, Mice, Benzodioxoles
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