Depression-like behaviour in rats with mononeuropathy is reduced by the CB2-selective agonist GW405833

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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 ± 2 g, CCI 12 ± 2 g; P < 0.001) and a significant increase in time of immobility (sham 133 ± 14 s, CCI 201 ± 9 s; P < 0.001). As time of swimming was unchanged, immobility was increased at the expense of climbing behaviour (sham 105 ± 17 s, CCI 63 ± 9 s; P < 0.05). There was no difference in ambulation between sham and CCI animals. In sham and CCI animals, desipramine (20 mg/kg) significantly reduced immobility (sham + vehicle 134 ± 19 s, sham + desipramine 79 ± 13 s; P < 0.01, CCI + vehicle 195 ± 8 s, CCI + desipramine 140 ± 11 s; P < 0.05) and increased climbing behaviour (sham + vehicle 118 ± 21 s, sham + desipramine 182 ± 16 s; P < 0.05, CCI + vehicle 59 ± 8 s, CCI + desipramine 112 ± 14 s; 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 ± 7 s, GW405833 145 ± 14 s; P < 0.01) and mechanical hypersensitivity (CCI + vehicle 15 ± 1 g, CCI + GW405833 24 ± 1 g; 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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