Concomitant use of tramadol and venlafaxine - evaluation of antidepressant-like activity and other behavioral effects in rats.

The aim of this study was to evaluate antidepressant-like effect (Porsolt test), locomotor activity and motor coordination of joint administration of tramadol (TRM) and venlafaxine (VEN) in rats. The tests were performed on male Wistar rats after single and chronic treatment (7 and 14 days) with TRM intraperitoneally (ip) and VEN orally (po) administered once a day. The controls were given 0.5% carboxymethylcellulose (CMC) solution (0.5 ml per rat, ip and po). It was found that combination of TRM (5 mg/kg ip) with VEN (20 mg/kg po) caused an increased antidepressant effect compared to TRM and VEN administered alone, with no effect on locomotor activity or motor coordination in rats, which may be of clinical significance. It was also observed that reduced time of active swimming of animals in Porsolt test with an increased dose (10 and 20 mg/kg) and time of administration (7 and 14 days) of TRM were correlated with a decreased locomotor activity in rats. It may indicate the development of tolerance to TRM's antidepressant effect in rats during chronic treatment with doses higher than 5 mg/kg. It can be expected that combination of low doses of TRM and VEN could potentially be feasible and relatively safe in cases with acute pain with co-existing depression, however, further investigations are needed.