The potentiation of analgesic activity of paracetamol plus morphine involves the serotonergic system in rat brain

Objective and Design: We investigated the antinociceptive effect of subactive doses of paracetamol and morphine, given in combination. Material and Treatment: Male Wistar rats were injected with paracetamol (50 or 100 mg/kg i.p.) and morphine (2, 3 or 5 mg/kg s.c.) 10 min later and subjected to algesimetric tests 20 min thereafter. Methods: Pain threshold was evaluated in the hot-plate and formalin tests. 5-HT2 receptor binding capacity and 5-HT and 5-HIAA levels were measured in cortical and pontine areas of the brain by means of radioligand binding technique and by HPLC, respectively. Statistical analysis was done using Student-Neuman-Keul's test and 2 x 2 factorial analysis. Results: Only when given in combination, paracetamol(100 mg/kg) and morphine (2 and 3 mg/kg) were able to evoke an antinociceptive effect in both tests associated with an increase in 5-HT levels and a decrease in 5-HT2 receptors In the cortex. These effects were prevented by i,p. pretreatment with naloxone (I mg/kg i.p,). Conclusions: Subactive doses of paracetamol and morphine exert an analgesic effect when given in combination in the rat and indicate an involvement of both serotonergic and opiatergic systems.