RT Journal Article
SR Electronic
T1 Regulation of CREB expression: in vivo evidence for a functional role in morphine action in the nucleus accumbens.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 306
OP 315
VO 276
IS 1
A1 K L Widnell
A1 D W Self
A1 S B Lane
A1 D S Russell
A1 V A Vaidya
A1 M J Miserendino
A1 C S Rubin
A1 R S Duman
A1 E J Nestler
YR 1996
UL http://jpet.aspetjournals.org/content/276/1/306.abstract
AB 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.