The effect of a paracetamol and morphine combination on dynorphin A levelsin the rat brain

The purpose of this study was to find our whether the combination of inacti ve doses of paracetamol (PARA) and morphine was able to change dynorphin (D YN) A levels, evaluated by radioimmunoassay, and whether naloxone or [(-)-2 -(3 furylmethyl)-normetazocine] (MR 2266), a kappa -opioid antagonist, modi fies or prevents the activity of this combination on nociception and on DYN levels. The work was suggested by our previous findings which demonstrated that inactive doses of PARA and morphine, when given in combination, share an antinociceptive effect, and that PARA, at, antinociceptive doses, decre ases DYN levels in the frontal cortex, thus indicating a selective action w ithin the CNS. Our present results demonstrate that the combination of inac tive doses of PARA (100 mg/kg) and morphine (3 mglkg) is just as effective in decreasing the levels of DYN A as full antinociceptive doses of PARA or morphine alone in the frontal cortex of the rat. The values, expressed in p mol/g tissue, were: control = 2.83 +/- 0.20; paracetamol (100) = 2.60 +/- 0 .23; morphine (3) = 2.73 +/- 0.24; paracetamol + morphine = 1.34 + 0.16 (P < 0.05), The decrease was partially antagonised by MR 2266, but not by nalo xone, suggesting that the activity of PARA and morphine in combination on D YN A levels could be mediated, at least in part, through K-receptors, altho ugh other systems may be involved. On the other hand, both naloxone and MR 2266 prevented the antinociceptive effect of the combination in the hot pla te test. All our experimental data suggest that PARA and morphine in combin ation exert their antinociceptive effect through the opioidergic system, wh ich in turn may cause a decrease in DYN levels in the CNS of the rat. <(c)> 2001 Elsevier Science Inc. All rights reserved.