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.

Depression-like behavior and mechanical allodynia are reduced by bis selenide treatment in mice with chronic constriction injury: a comparison with fluoxetine, amitriptyline, and bupropion

“…The results demonstrated in this study confirmed previous data (Gonçalves et al 2008;Hu et al 2009) in which rodents display depressive-like behavior induced by nerve injury. The data demonstrate an important dissociation between the antiallodynic and antidepressant effects in mice when tested in a model of neuropathic pain.…”

“…Treatment with amitriptyline also showed antidepressant-like effect in sham-operated mice. These results were corroborated by Hu et al (2009) who demonstrated that desipramine (20 mg/kg) reduced the depression-like behavior in rats with mononeuropathy. In a number of neuropathic pain conditions, their analgesic action has been demonstrated to be independent of mood alteration (Max et al 1987;Wolfe and Trivedi 2004;Sindrup et al 2005).…”

Validation of an air-puff passive-avoidance paradigm for assessment of aversive learning and memory in rat models of chronic pain

“…Our results suggest that aversive learning and memory assessed in our air-puff passive-avoidance paradigm were not affected in either the inflammatory (CFA) or neuropathic (SNL) pain models under the conditions and at the time-point described. This result supports the findings of Suzuki et al (2007) and other related research which has shown that learned helplessness in the forcedswim test and active avoidance in the place-escape/avoidance paradigm can be acquired in rat models of chronic pain (Goncalves et al, 2008;Hu et al, 2009;Leite-Almeida et al, 2009;Suzuki et al, 2007). These findings relating to aversive learning and memory are somewhat surprising given the evidence, discussed above, that chronic pain is associated with impairment in other cognitive domains, both clinically and preclinically.…”

The CGRP receptor antagonist BIBN4096BS peripherally alleviates inflammatory pain in rats

“…Experiments were done 24 h after CFA injection. Surgeries were done under isoflurane anaesthesia and followed procedures described earlier [30,58]. The control group of animals was naive to therapy and received no injections into the paw.…”