Effect of acute and repeated administration of paracetamol on opioidergic and serotonergic systems in rats

We investigated the antinociceptive effect of paracetamol or morphine after repeated administration and the changes in the characteristics of central mu-, kappa- and 5-HT2 receptors.

Male rats were injected twice a day for seven days with paracetamol (400 mg/kg, i. p.) or morphine (5 mg/kg, s. c.).

The antinociceptive effect was evaluated 30 min after single and multiple doses of paracetamol and morphine through the hot-plate test. Binding techniques were used to evaluate the receptor characteristics in the frontal cortex.

Both paracetamol and morphine induced an antinociceptive effect on day 1 but only paracetamol maintained this effect for seven days while morphine did not. The number of mu-opioid receptors decreased on days 1, 3, and 7 by a similar percentage after paracetamol administration (by 29, 31 and 34 %, respectively), while morphine produced a progressive decrease in comparison with controls (by 37, 49 and 60 %, respectively) and kappa-opioid receptors were unaffected. Both drugs similarly decreased the 5-HT2 receptor number on all days of treatment (by about 30 %).

The opioidergic and serotonergic systems are involved in different ways in the induction and maintenance of antinociception after paracetamol or morphine treatment.