Regulation of CREB expression: in vivo evidence for a functional role in morphine action in the nucleus accumbens - PubMed (original) (raw)

. 1996 Jan;276(1):306-15.

Affiliations

PMID: 8558448

Regulation of CREB expression: in vivo evidence for a functional role in morphine action in the nucleus accumbens

K L Widnell et al. J Pharmacol Exp Ther. 1996 Jan.

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 anti-sense 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.

PubMed Disclaimer

Cited by

Therapeutic targeting of "DARPP-32": a key signaling molecule in the dopiminergic pathway for the treatment of opiate addiction.
Mahajan SD, Aalinkeel R, Reynolds JL, Nair BB, Sykes DE, Hu Z, Bonoiu A, Ding H, Prasad PN, Schwartz SA. Mahajan SD, et al. Int Rev Neurobiol. 2009;88:199-222. doi: 10.1016/S0074-7742(09)88008-2. Int Rev Neurobiol. 2009. PMID: 19897079 Free PMC article.
Dopamine-dependent increases in phosphorylation of cAMP response element binding protein (CREB) during precipitated morphine withdrawal in primary cultures of rat striatum.
Chartoff EH, Papadopoulou M, Konradi C, Carlezon WA Jr. Chartoff EH, et al. J Neurochem. 2003 Oct;87(1):107-18. doi: 10.1046/j.1471-4159.2003.01992.x. J Neurochem. 2003. PMID: 12969258 Free PMC article.
The neuropeptide Y Y1 receptor knockdown modulates activator protein 1-involved feeding behavior in amphetamine-treated rats.
Hsieh YS, Chen PN, Yu CH, Liao JM, Kuo DY. Hsieh YS, et al. Mol Brain. 2013 Nov 13;6:46. doi: 10.1186/1756-6606-6-46. Mol Brain. 2013. PMID: 24225225 Free PMC article.
Sex-Specific Effects of Stress on Mood-Related Gene Expression.
Barko K, Paden W, Cahill KM, Seney ML, Logan RW. Barko K, et al. Mol Neuropsychiatry. 2019 Jun;5(3):162-175. doi: 10.1159/000499105. Epub 2019 Apr 30. Mol Neuropsychiatry. 2019. PMID: 31312637 Free PMC article.
cAMP response element-binding protein in the amygdala is required for long- but not short-term conditioned taste aversion memory.
Lamprecht R, Hazvi S, Dudai Y. Lamprecht R, et al. J Neurosci. 1997 Nov 1;17(21):8443-50. doi: 10.1523/JNEUROSCI.17-21-08443.1997. J Neurosci. 1997. PMID: 9334416 Free PMC article.

Regulation of CREB expression: in vivo evidence for a functional role in morphine action in the nucleus accumbens - PubMed (original) (raw)