Document Detail

Phosphodiesterase 4 inhibitors, rolipram and diazepam block the adaptive changes observed during morphine withdrawal in the heart.
MedLine Citation:
PMID:  17601555     Owner:  NLM     Status:  MEDLINE    
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.
Ana González-Cuello; Lorenzo Sánchez; Jesús Hernández; M Teresa Castells; M Victoria Milanés; M Luisa Laorden
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-06-09
Journal Detail:
Title:  European journal of pharmacology     Volume:  570     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-08-20     Completed Date:  2007-11-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1-9     Citation Subset:  IM    
Department of Pharmacology, University School of Medicine, 30100 Murcia, Spain.
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MeSH Terms
Cyclic AMP / metabolism
Cyclic GMP / metabolism
Cyclic Nucleotide Phosphodiesterases, Type 4 / antagonists & inhibitors
Diazepam / therapeutic use*
Morphine Dependence / drug therapy,  metabolism
Myocardium / metabolism*
Norepinephrine / metabolism
Normetanephrine / metabolism
Phosphodiesterase Inhibitors / therapeutic use*
Proto-Oncogene Proteins c-fos / metabolism
Rats, Sprague-Dawley
Rolipram / therapeutic use*
Substance Withdrawal Syndrome / drug therapy*,  metabolism
Reg. No./Substance:
0/Phosphodiesterase Inhibitors; 0/Proto-Oncogene Proteins c-fos; 439-14-5/Diazepam; 51-41-2/Norepinephrine; 60-92-4/Cyclic AMP; 61413-54-5/Rolipram; 7665-99-8/Cyclic GMP; 97-31-4/Normetanephrine; EC Nucleotide Phosphodiesterases, Type 4

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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