Depression-like behaviour in rats with mononeuropathy is reduced by the CB2-selective agonist GW405833
Abstract
The current study assessed whether the chronic constriction injury (CCI) model of neuropathic pain causes depression-like behaviour in animals, and if this depression-like behaviour can be reversed by anti-nociceptive and/or antidepressant drugs. CCI of the sciatic nerve in rats was selected as a neuropathic pain model, mechanical hypersensitivity was assessed by punctuate mechanical stimuli, and depression-like behaviour was evaluated in the forced swimming test (FST) measuring the time of immobility, climbing and swimming. The CCI rats displayed a significant mechanical hypersensitivity (sham 27+/-2g, CCI 12+/-2g; P<0.001) and a significant increase in time of immobility (sham 133+/-14s, CCI 201+/-9s; P<0.001). As time of swimming was unchanged, immobility was increased at the expense of climbing behaviour (sham 105+/-17s, CCI 63+/-9s; P<0.05). There was no difference in ambulation between sham and CCI animals. In sham and CCI animals, desipramine (20mg/kg) significantly reduced immobility (sham+vehicle 134+/-19s, sham+desipramine 79+/-13s; P<0.01, CCI+vehicle 195+/-8s, CCI+desipramine 140+/-11s; P<0.05) and increased climbing behaviour (sham+vehicle 118+/-21s, sham+desipramine 182+/-16s; P<0.05, CCI+vehicle 59+/-8s, CCI+desipramine 112+/-14s; P<0.05) with little effect on mechanical hypersensitivity. In contrast in CCI animals the cannabinoid CB2-selective agonist GW405833 (2,3-dichloro-phenyl)-[5-methoxy-2-methyl-3-(2-morpholin-4-yl-ethyl)-indol-1-yl]-methanone) (30 mg/kg) significantly attenuated immobility (CCI+vehicle 191+/-7s, GW405833 145+/-14s; P<0.01) and mechanical hypersensitivity (CCI+vehicle 15+/-1g, CCI+GW405833 24+/-1g; P<0.001). Moreover, differently from desipramine, GW405833 did not change the climbing behaviour. These data suggest that rats subjected to the CCI model of neuropathic pain develop depression-like behaviour, which can be reversed by appropriate anti-nociceptive treatment.
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GW405833, a CB2-specific agonist, reduces depression-like behavior associated with mononeuropathy in the forced swim test.
“Interestingly, GW405833, a CB2-specific agonist, also reduces depression-like behavior associated with this mononeuropathy in the forced swim test.50”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [50]
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- Authors
- Hu, B., Doods, H., Treede, R.-D., & Ceci, A.
- Affiliations
- Boehringer Ingelheim (Germany) (DE)
- Heidelberg University (DE)
- Corresponding author
- Ceci, Angelo
- Venue
- Pain
- Published
- 2009-06
- Volume
- 143
- Issue
- 3
- Pages
- 206-212
- ISSN
- 0304-3959 (ISSN-L)
- OpenAlex
- W2001545679
- Cited by
- 138
- References
- 44
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 11 · 2020: 17 · 2019: 8 · 2018: 6 · 2017: 6 · 2016: 8 · 2015: 15 · 2014: 9 · 2013: 11 · 2012: 6
- FWCI
- 5.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pain (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bundesministerium für Bildung und Forschung
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- CB2 receptor agonist, neuropathic pain, depression-like behavior, chronic constriction injury, sciatic nerve, forced swim test, immobility, desipramine, mechanical hypersensitivity, cannabinoid therapy, antidepressant effects, nociception, rats, pain-depression comorbidity, neuroinflammation, neuroprotection, neurogenesis, neuroplasticity
- MeSH terms
- Animals, Antidepressive Agents, Antidepressive Agents, Tricyclic, Behavior, Animal, Depressive Disorder, Desipramine, Disease Models, Animal, Exploratory Behavior, Hyperalgesia, Indoles, Ligation, Male, Morpholines, Motor Activity, Neuralgia, Neuropsychological Tests, Pain Measurement, Peripheral Nervous System Diseases, Swimming, Treatment Outcome, Rats, Wistar, Sciatic Neuropathy, Receptor, Cannabinoid, CB2, Rats
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