Regulation of CREB expression

In vivo evidence for a functional role in morphine action in the nucleus accumbens

Katherine L. Widnell, David W. Self, Sarah B. Lane, David S. Russell, Vidita A. Vaidya, Mindy J D Miserendino, Charles S. Rubin, Ronald S. Duman, Eric J. Nestler

Research output: Contribution to journalArticle

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Abstract

Previous work has shown that chronic opiate administration regulates protein components of the cAMP signaling pathway, specifically in the nucleus accumbens (NAc), a brain region implicated in the reinforcing properties of opiates, and that such adaptations may contribute to changes in reinforcement mechanisms that characterize opiate addiction. In the present study, we examined a possible role for the transcription factor cAMP response element- binding protein (CREB) in mediating these long-term effects of opiates in the NAc. Chronic, but not acute, morphine administration was found to decrease levels of CREB immunoreactivity in the NAc, an effect not seen in other brain regions studied. The functional significance of this CREB down-regulation was then investigated by the use of an antisense oligonucleotide strategy that produces a specific and sustained decrease in CREB levels in the NAc, without detectable toxicity. It was found that the antisense oligonucleotide-induced reduction in CREB levels mimicked the effect of morphine on certain, but not all, cAMP pathway proteins in this brain region, whereas a large number of other signal transduction proteins tested were unaffected by this treatment. Our results support a role for CREB in autoregulation of the cAMP pathway in the nervous system, as well as in mediating some of the effects of morphine on this signaling pathway in the NAc.

Original languageEnglish (US)
Pages (from-to)306-315
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Volume276
Issue number1
StatePublished - Jan 1996

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Cyclic AMP Response Element-Binding Protein
Nucleus Accumbens
Morphine
Opiate Alkaloids
Antisense Oligonucleotides
Brain
Opioid-Related Disorders
Proteins
Nervous System
Signal Transduction
Homeostasis
Transcription Factors
Down-Regulation

ASJC Scopus subject areas

  • Pharmacology

Cite this

Widnell, K. L., Self, D. W., Lane, S. B., Russell, D. S., Vaidya, V. A., Miserendino, M. J. D., ... Nestler, E. J. (1996). Regulation of CREB expression: In vivo evidence for a functional role in morphine action in the nucleus accumbens. Journal of Pharmacology and Experimental Therapeutics, 276(1), 306-315.

Regulation of CREB expression : In vivo evidence for a functional role in morphine action in the nucleus accumbens. / Widnell, Katherine L.; Self, David W.; Lane, Sarah B.; Russell, David S.; Vaidya, Vidita A.; Miserendino, Mindy J D; Rubin, Charles S.; Duman, Ronald S.; Nestler, Eric J.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 276, No. 1, 01.1996, p. 306-315.

Research output: Contribution to journalArticle

Widnell, KL, Self, DW, Lane, SB, Russell, DS, Vaidya, VA, Miserendino, MJD, Rubin, CS, Duman, RS & Nestler, EJ 1996, 'Regulation of CREB expression: In vivo evidence for a functional role in morphine action in the nucleus accumbens', Journal of Pharmacology and Experimental Therapeutics, vol. 276, no. 1, pp. 306-315.
Widnell, Katherine L. ; Self, David W. ; Lane, Sarah B. ; Russell, David S. ; Vaidya, Vidita A. ; Miserendino, Mindy J D ; Rubin, Charles S. ; Duman, Ronald S. ; Nestler, Eric J. / Regulation of CREB expression : In vivo evidence for a functional role in morphine action in the nucleus accumbens. In: Journal of Pharmacology and Experimental Therapeutics. 1996 ; Vol. 276, No. 1. pp. 306-315.
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