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) (30mg/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.

Keywords: Neuropathic pain, Depression-like behaviour, Comorbidity, Animal models