The antinociceptive effect of morphine is reversed by okadaic acid in morphine-naive but not in morphine-tolerant mice

  • Ocaña M
  • Entrena J
  • Baeyens J
 et al. 
  • 6


    Mendeley users who have this article in their library.
  • 3


    Citations of this article.


The activation of specific subtypes of serine/threonine protein phosphatases (PPs) plays a role in the antinociceptive effect of acute morphine, but it is not known whether these enzymes are involved in morphine-induced antinociception in morphine-tolerant animals. We evaluated the effects of both okadaic acid (a selective inhibitor of some serine/threonine PPs) and its inactive analogue L-norokadaone on the antinociception induced by morphine in morphine-naive and -tolerant female mice in the tail-flick test. Okadaic acid (0.01 and 1 pg/mouse, i.c.v.), but not L-norokadaone (1 pg/mouse, i.c.v.), antagonized in a dose-dependent way the antinociception induced by morphine (1-16 mg/kg, s.c.) in morphine-naive animals. However, both okadaic acid (0.01 and 1 pg/mouse, i.c.v.) and L-norokadaone (1 pg/mouse, i.c.v.) were unable to modify the antinociceptive effect of morphine in morphine-tolerant mice. These results suggest that in morphine-induced thermal analgesia, the role of serine/threonine PPs highly sensitive to okadaic acid is different in morphine-tolerant and morphine-naive female mice. © 2007 Elsevier Inc. All rights reserved.

Author-supplied keywords

  • Antinociception
  • L-norokadaone
  • Morphine tolerance
  • Okadaic acid
  • Serine/threonine protein phosphatases

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document


  • María Ocaña

  • José M. Entrena

  • José M. Baeyens

  • Esperanza Del Pozo

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free