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Precipitated morphine withdrawal stimulates multiple activator protein- 1 signaling pathways in rat brain

P Couceyro and J Douglass

Vollum Institute, Oregon Health Sciences University, Portland 97201.

Morphine dependence is a long lasting form of neuronal plasticity. Naloxone-precipitated morphine withdrawal, a model of opioid dependence, induces brain region-specific changes in activator protein- 1 (AP-1) transcription factor gene expression. Rapid increases in c- fos, fos-B, jun-B, and c-jun mRNA levels accompany withdrawal, with the relative level of induction correlating with the severity of physical dependence. Altered patterns of c-fos mRNA expression were limited to neuronal circuits mediating stress responses, motivation, and cognition. AP-1 DNA-binding activity and dimer composition also exhibited regulation after withdrawal, presumably as a result of both transcriptional and post-translational events. Thus, morphine dependence results in the alteration of diverse, brain region-specific, signal transcription pathways involving AP-1 transcription factors.

Volume 47, Issue 1, pp. 29-39, 01/01/1995
Copyright © 1995 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1995 by the American Society for Pharmacology and Experimental Therapeutics