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.

• Authors: Bing Hu, Henri Doods, Rolf-Detlef Treede, Angelo Ceci
• Journal: Pain (Pain) Vol. 143 Issue 3 Pg. 206-212 (Jun 2009) ISSN: 1872-6623 [Electronic] United States
• PMID: 19345493 (Publication Type: Journal Article)

Chemical References

• 1-(2,3-dichlorobenzoyl)-5-methoxy-2-methyl-(2-(mopholin-4-yl)ethyl)-1H-indole
• Antidepressive Agents
• Antidepressive Agents, Tricyclic
• Cnr2 protein, rat
• Indoles
• Morpholines
• Receptor, Cannabinoid, CB2
• Desipramine

Topics

• Animals
• Antidepressive Agents (pharmacology, therapeutic use)
• Antidepressive Agents, Tricyclic (pharmacology)
• Behavior, Animal (drug effects, physiology)
• Depressive Disorder (drug therapy, etiology, psychology)
• Desipramine (pharmacology)
• Disease Models, Animal
• Exploratory Behavior (drug effects, physiology)
• Hyperalgesia (complications, psychology)
• Indoles (pharmacology, therapeutic use)
• Ligation (adverse effects)
• Male
• Morpholines (pharmacology, therapeutic use)
• Motor Activity (drug effects, physiology)
• Neuralgia (complications, psychology)
• Neuropsychological Tests
• Pain Measurement (methods)
• Peripheral Nervous System Diseases (complications, psychology)
• Rats
• Rats, Wistar
• Receptor, Cannabinoid, CB2 (agonists, metabolism)
• Sciatic Neuropathy (complications, psychology)
• Swimming (psychology)
• Treatment Outcome