Phosphodiesterase 4 inhibitors, rolipram and diazepam block the adaptive changes observed during morphine withdrawal in the heart

  • González-Cuello A
  • Sánchez L
  • Hernández J
 et al. 
  • 2

    Readers

    Mendeley users who have this article in their library.
  • 10

    Citations

    Citations of this article.

Abstract

In this study, we investigated whether morphine dependence was inhibited by phosphodiesterase (PDE) 4 inhibitors rolipram and diazepam, since a role for the cyclic AMP systems in the development of morphine dependence was reported. Dependence of morphine was induced by a 7-day s.c. implantation of morphine pellets. Morphine withdrawal was precipitated on day 8 by an injection of naloxone. In order to determine the effect of rolipram or diazepam the animals were injected with these drugs for seven days and 30 min before the administration of naloxone. When opioid withdrawal was precipitated, enhancement of noradrenaline (NA) turnover in the heart was observed 30 min after naloxone administration. Moreover, morphine withdrawal induces Fos expression, increase in cyclic AMP and cyclic GMP levels. Co-administration of rolipram or diazepam with morphine during the pre-treatment period significantly reduces the signs of withdrawal symptoms, the enhancement of NA turnover, the increase in cyclic AMP and the Fos expression. However, these inhibitors did not modify the levels of cyclic GMP. These findings demonstrated that co-administration of rolipram or diazepam with morphine abolish the development of morphine dependence and suggest that these compounds prevent the up-regulation of the cyclic AMP pathway and the associated increase in cyclic AMP level after naloxone administration. © 2007 Elsevier B.V. All rights reserved.

Author-supplied keywords

  • Cyclic AMP
  • Cyclic GMP
  • Diazepam
  • Fos
  • Heart
  • Morphine-withdrawal
  • Noradrenaline turnover
  • Rolipram

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

Authors

  • Ana González-CuelloUniversidad de Murcia

    Follow
  • Lorenzo Sánchez

  • Jesús Hernández

  • M. Teresa Castells

  • M. Victoria Milanés

  • M. Luisa Laorden

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free