Depression-like behaviour in rats with mononeuropathy is reduced by the CB2-selective agonist GW405833.
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.
Department of CNS Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Straße 65, 88397 Biberach an der Riss, Germany Chair of Neurophysiology, Center for Biomedicine and Medical Technology Mannheim (CBTM), Ruprecht-Karls-University Heidelberg, Ludolf-Krehl-Straße 13-17, 68167 Mannheim, Germany.
Bing
B
Hu
Henri
H
Doods
Rolf-Detlef
RD
Treede
Angelo
A
Ceci
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003866:Depressive Disorder / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology*; D003891:Desipramine / Q000494:pharmacology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D006930:Hyperalgesia / Q000150:complications / Q000523:psychology; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D008026:Ligation / Q000009:adverse effects; D008297:Male; D009025:Morpholines / Q000494:pharmacology* / Q000627:therapeutic use; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009437:Neuralgia / Q000150:complications / Q000523:psychology*; D009483:Neuropsychological Tests; D010147:Pain Measurement / Q000379:methods; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000523:psychology*; D051381:Rats; D017208:Rats, Wistar; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000378:metabolism; D020426:Sciatic Neuropathy / Q000150:complications / Q000523:psychology; D013550:Swimming / Q000523:psychology; D016896:Treatment Outcome
C463040:1-(2,3-dichlorobenzoyl)-5-methoxy-2-methyl-(2-(mopholin-4-yl)ethyl)-1H-indole; D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; C469526:Cnr2 protein, rat; D007211:Indoles; D009025:Morpholines; D043885:Receptor, Cannabinoid, CB2; D003891:Desipramine