C-type natriuretic peptide can modify the acute and chronic effects of morphine

Different doses (0.2-200 ng) of C-type natriuretic peptide (CNP) were administered into the lateral brain ventricle, and morphine (5 mg/kg) was injected subcutaneously. The analgesic effect was measured in a tail-flick test, in CFLP mice. CNP administered centrally did not itself affect pain sensitivity, but it depressed the acute antinociceptive effect of morphine 30 min after icv (0.2, 2 or 20 ng) CNP administration and the 2 and 20 ng doses also decreased this action after 60 min. CNP in a 0.2 or 200 ng dose blocked the development of acute tolerance to morphine after 30 min, as did the 200 ng dose at 60 min. CNP in a 0.2 ng dose blocked the development of chronic tolerance to morphine after 30 min, but there was no effect at 60 min. Morphine withdrawal signs were studied by injecting naloxone (1 mg/kg sc). There was no significant difference in symptoms between the tolerant group and the animals treated with CNP.