author(s)
Salma J Askar, Amer H Chyad and Omar SI Al-Janabi

abstract
Tramadol is a centrally acting analgesic drug which is used for treating moderate to severe pain. It is a synthetic opioid which binds weakly to micro (μ) opioid receptor. Several studies have recommended that both opioid and monoaminergic systems play a role in depression which is the disease that occurring due to deficit of norepinephrine and serotonin. Tramadol inhibits the re uptake of norepinephrine and serotonin in the synaptic cleft. The present study was carried out to evaluate the involvement of the interaction of serotonin and noradrenaline in the antidepressant-like effect of tramadol using tail-suspension test (TST) and forced swim test (FST) in acute and after 15 days of treatments. In acute studies (7 days), animals were divided into six groups and each group comprised of six mice. Group 1 was pretreated with normal saline which served as negative control. Group2 was pretreated with standard antidepressant drug imipramine (positive control) at a dose of 10 mg/kg whereas Group 3 and 4 were pretreated with two different doses (20 and 40 mg/kg) of tramadol. Group 5 was treated with a combination of ondansetron 4 mg/kg + tramadol 40 mg/kg while the Group 6 was pretreated with a combination of terazosin 1 mg/kg + tramadol 40 mg/kg. All these drugs were given intraperitoneally (0.1 ml/10gm) for both acute and after 15 days of treatments. Fifteen-minutes of drug administration, the immobility times (seconds) of treated mice were recorded in TST and FST. In the next stage of study after 15 days of treatment procedures were performed with six different groups of mice each group comprising of six mice and arrangement of groups are the same as that in acute study. The results showed that tramadol at a dose of 40 mg/kg significantly (P<0.05) decreased immobility times in both TST and FST in acute and after 15 days of treatment as compared to control group. There were no significant differences in the antidepressant effect in mice administered with tramadol 40 mg/kg and imipramine 10 mg/kg. Ondansetron and terazosin increase the immobility times in both tests when they were given in combination with tramadol 40 mg/kg.It can be concluded that tramadol has the antidepressant-like effect in standard models of depression and the antidepressant activity of tramadol is mediated through the mechanisms that involved serotonergic and noradrenergic systems.