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

Objective and design: We investigated the antinociceptiveeffect of paracetamol or morphine after repeatedadministration and the changes in the characteristics of centralμ-, κ- and 5-HT2 receptors.Treatment: Male rats were injected twice a day for sevendays with paracetamol (400 mg/kg, i. p.) or morphine (5 mg/kg, s. c.).Methods: The antinociceptive effect was evaluated 30 minafter single and multiple doses of paracetamol and morphinethrough the hot-plate test. Binding techniques were used toevaluate the receptor characteristics in the frontal cortex.Results: Both paracetamol and morphine induced an antinociceptiveeffect on day 1 but only paracetamol maintainedthis 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 morphineproduced a progressive decrease in comparison with controls(by 37, 49 and 60 %, respectively) and κ-opioid receptorswere unaffected. Both drugs similarly decreased the 5-HT2receptor number on all days of treatment (by about 30 %).Conclusions: The opioidergic and serotonergic systems areinvolved in different ways in the induction and maintenanceof antinociception after paracetamol or morphine treatment.