Evaluation of Anti-depressant and Analgesic- Like Activity of Ondansetron in Rodents Model of Co-morbid Pain and Depression

Abstract:

Although a clinical connection between pain and depression has long been recognized, how these two conditions interact remains unclear. Here we report the comorbidity of pain and depression-like behavior. The antidepressant and analgesic like activity of Ondansetron (OND, 0.25-2mg/kg) were investigated in animal models of acute depression (forced swim test ) and pain ( tail flick test) , existence of co-morbidity of pain and depression was simulated in surgical models in rats like olfactory bulbectomy (OBX) model of chronic depression and chronic constrictive injury (CCI) of chronic pain conditions. Acute administration of OND (0.5-2mg/kg i.p) significantly reduced the duration of immobility in mice in FST and increased the time latency in tail flick test. Behavioural anomalies shown by OBX rats in open field test was significantly reversed by OND (1-2 mg/kg p.o) but OBX rats failed to show the any kind of nociception. Further OND successfully reversed pain in CCI rats. In addition to reversal of pain, OND (1-2mg/kg p.o) significantly reduced the hyperactivity exhibited by CCI rats in open field test suggesting the effect of OND in co-morbid pain and depression. OND exhibited significant antidepressant and analgesic like effect as indicated by its ability to reduce swim stress induced immobility and reduction in writhing. The present study showed that OND has equal efficacy in comorbid pain and depression-like behavioural mediated through serotonergic system.

Keywords: Comorbidity, Pain, Depression, 5-HT₃ Antagonist