Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Phosphodiesterase 4 inhibitors, rolipram and diazepam block the adaptive changes observed during morphine withdrawal in the heart. 1760 55

A role for the cyclic AMP systems in the development of morphine dependence has been previously reported. In this study we investigated whether morphine dependence was inhibited by phosphodiesterase (PDE) 4 inhibitors rolipram and diazepam. Dependence on morphine was induced by a 7-day s.c. implantation of morphine pellets. On day 8, morphine withdrawal was precipitated by an injection of naloxone. In order to determine the effect of rolipram and diazepam rats were injected with these drugs once daily for seven days as well as 30 min before of naloxone injection. When opioid withdrawal was precipitated, an enhanced noradrenaline turnover and increased level of cyclic AMP and cyclic GMP in the hypothalamic paraventricular nucleus (PVN) were observed 30 min after naloxone administration. Moreover, c-Fos expression was induced in the PVN after naloxone-precipitated morphine withdrawal. Co-administration of rolipram or diazepam with morphine during the pre-treatment period, significantly reduced the signs of withdrawal, the enhancement of noradrenaline turnover and the increase in cyclic AMP. However, these inhibitors did not modify either levels of cyclic GMP or c-Fos expression in the PVN. These findings demonstrate that co-administration of rolipram or diazepam with morphine attenuate the withdrawal syndrome and suggest that these compounds may prevent the up-regulation of the cyclic AMP pathway and the associated increase in cyclic AMP level in morphine-withdrawn rats.
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PMID:Effects of rolipram and diazepam on the adaptive changes induced by morphine withdrawal in the hypothalamic paraventricular nucleus. 1968 23