Effects of morphine on forskolin-stimulated pro-enkephalin mRNA levels in rat striatum: a model for acute and chronic opioid actions in brain

Bryan W. Kluttz, Kent Vrana, Steven I. Dworkin, Steven R. Childers

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Opioid agonists inhibit adenylyl cyclase in brain through Gi-coupled receptors. One potential biological role for this reaction would be to decrease pro-enkephalin mRNA synthesis by decreasing intracellular cAMP levels and preventing stimulation of gene expression via the cAMP regulatory element (CRE). To determine whether such effects occur in vivo, rats were injected i.c.v. with a water-soluble analog of forskolin, 7-0-deacetyl-7β[γ-(morpholino)-butyryl] forskolin (DMB-forskolin), to stimulate the CRE. Pro-enkephalin mRNA levels were assayed in striatum by Northern blot analysis. The treatment with the forskolin analog increased striatal pro-enkephalin mRNA levels approximately 2-fold in 4 h. When rats were injected with morphine (20 mg/kg i.p.) 1 h before DMB-forskolin administration, the stimulation of pro-enkephalin mRNA levels was eliminated. This acute effect of morphine was blocked by co-administration with 10 mg/kg naloxone. When rats were chronically treated with morphine for 8 days, then injected with morphine (20 mg/kg i.p.) 1 h before DMB-forskolin administration, the inhibitory effect of morphine was lost (i.e. DMB-forskolin increased pro-enkephalin mRNA levels by 2 fold in either control and morphine-treated rats). These data not only demonstrate the in vivo relevance of opioid-inhibited adenylyl cyclase in the control of pro-enkephalin mRNA levels, but also show that this model is useful for studying how this signal transduction system is attenuated during the development of tolerance.

Original languageEnglish (US)
Pages (from-to)313-320
Number of pages8
JournalMolecular Brain Research
Volume32
Issue number2
DOIs
StatePublished - Jan 1 1995

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Colforsin
Morphine
Opioid Analgesics
Morpholinos
Messenger RNA
Brain
Adenylyl Cyclases
Corpus Striatum
Naloxone
Northern Blotting
proenkephalin
Signal Transduction
Gene Expression
Water

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

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title = "Effects of morphine on forskolin-stimulated pro-enkephalin mRNA levels in rat striatum: a model for acute and chronic opioid actions in brain",
abstract = "Opioid agonists inhibit adenylyl cyclase in brain through Gi-coupled receptors. One potential biological role for this reaction would be to decrease pro-enkephalin mRNA synthesis by decreasing intracellular cAMP levels and preventing stimulation of gene expression via the cAMP regulatory element (CRE). To determine whether such effects occur in vivo, rats were injected i.c.v. with a water-soluble analog of forskolin, 7-0-deacetyl-7β[γ-(morpholino)-butyryl] forskolin (DMB-forskolin), to stimulate the CRE. Pro-enkephalin mRNA levels were assayed in striatum by Northern blot analysis. The treatment with the forskolin analog increased striatal pro-enkephalin mRNA levels approximately 2-fold in 4 h. When rats were injected with morphine (20 mg/kg i.p.) 1 h before DMB-forskolin administration, the stimulation of pro-enkephalin mRNA levels was eliminated. This acute effect of morphine was blocked by co-administration with 10 mg/kg naloxone. When rats were chronically treated with morphine for 8 days, then injected with morphine (20 mg/kg i.p.) 1 h before DMB-forskolin administration, the inhibitory effect of morphine was lost (i.e. DMB-forskolin increased pro-enkephalin mRNA levels by 2 fold in either control and morphine-treated rats). These data not only demonstrate the in vivo relevance of opioid-inhibited adenylyl cyclase in the control of pro-enkephalin mRNA levels, but also show that this model is useful for studying how this signal transduction system is attenuated during the development of tolerance.",
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Effects of morphine on forskolin-stimulated pro-enkephalin mRNA levels in rat striatum : a model for acute and chronic opioid actions in brain. / Kluttz, Bryan W.; Vrana, Kent; Dworkin, Steven I.; Childers, Steven R.

In: Molecular Brain Research, Vol. 32, No. 2, 01.01.1995, p. 313-320.

Research output: Contribution to journalArticle

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AU - Vrana, Kent

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