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

Abstract.

Objective and design:

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

Treatment:

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

Methods:

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.

Results:

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 μ-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 κ-opioid receptors were unaffected. Both drugs similarly decreased the 5-HT₂ receptor number on all days of treatment (by about 30 %).

Conclusions:

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