Monoacylglycerol lipase inhibition-induced changes in plasma corticosterone levels, anxiety and locomotor activity in male CD1 mice
Open accessAbstract
The hypothalamus-pituitary-adrenal-axis is strongly controlled by the endocannabinoid system. The specific impact of enhanced 2-arachidonoylglycerol signaling on corticosterone plasma levels, however, was not investigated so far. Here we studied the effects of the recently developed monoacylglycerol lipase inhibitor JZL184 on basal and stress-induced corticosterone levels in male CD1 mice, and found that this compound dramatically increased basal levels without affecting stress responses. Since acute changes in corticosterone levels can affect behavior, JZL184 was administered concurrently with the corticosterone synthesis inhibitor metyrapone, to investigate whether the previously shown behavioral effects of JZL184 are dependent on corticosterone. We found that in the elevated plus-maze, the effects of JZL184 on "classical" anxiety-related measures were abolished by corticosterone synthesis blockade. By contrast, effects on the "ethological" measures of anxiety (i.e. risk assessment) were not affected by metyrapone. In the open-field, the locomotion-enhancing effects of the compound were not changed either. These findings show that monoacylglycerol lipase inhibition dramatically increases basal levels of corticosterone. This endocrine effect partly affects the anxiolytic, but not the locomotion-enhancing effects of monoacylglycerol lipase blockade.
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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., 2013
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The endocannabinoid system as a target for novel anxiolytic drugs
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- Authors
- Aliczki, M., Zelena, D., Mikics, E., Varga, Z. K., Pinter, O., Bakos, N. V., Varga, J., & Haller, J.
- Affiliations
- HUN-REN Institute of Experimental Medicine (HU)
- ORCID
- Varga, Janos
- Venue
- Hormones and Behavior
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 63
- Issue
- 5
- Pages
- 752-758
- ISSN
- 0018-506X (ISSN-L)
- OpenAlex
- W2036973557
- Cited by
- 50
- References
- 46
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 7 · 2020: 4 · 2019: 2 · 2018: 5 · 2017: 4 · 2016: 6 · 2015: 7 · 2014: 2 · 2013: 2
- FWCI
- 4.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hormones and Behavior (publishedVersion)
- PubMed (publishedVersion)
- Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
- Funders
- Hungarian Scientific Research Fund (OTKA) (72621, 101645)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- monoacylglycerol lipase inhibition, JZL184, 2-arachidonoylglycerol, endocannabinoid system, corticosterone, hypothalamic-pituitary-adrenal axis, anxiety, locomotor activity, metyrapone, stress response, risk assessment, anxiolytic effects
- MeSH terms
- Animals, Anxiety, Corticosterone, Enzyme Inhibitors, Male, Metyrapone, Monoacylglycerol Lipases, Motor Activity, Piperidines, Mice, Benzodioxoles
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