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Publication . Article . 1998

Cocaine and the AP-1 Transcription Factor Complex

Bruce T. Hope;
Open Access
Published: 01 May 1998 Journal: Annals of the New York Academy of Sciences, volume 844, pages 1-6 (issn: 0077-8923, Copyright policy )
Publisher: Wiley
Abstract

Cocaine addition in humans develops gradually with repeated administrations and persists long after cocaine has cleared the body. The mechanisms underlying this persistent form of neuroplasticity are not understood and can involve both structural and biochemical mechanisms. The long time course for cocaine addiction in humans and for development of cocaine self-administration in animal models suggest the involvement of alterations in gene expression leading to altered signaling in the brain. In the striatum (Str) and nucleus accumbens (NAc) of rats. Pretreatment with repeated cocaine administrations downregulates the induction of various immediate early genes (IEGs) by a subsequent acute challenge with cocaine. Some of these downregulated IEGs encode Fos-related components of the activator protein-1 (AP-1) complex, which is likely re regulate a number of genes important for neuronal function. Interestingly, repeated cocaine administration induces novel delta FosB-related proteins (called chronic Fos-related antigens (Fras)) in the NAc and Str that replace the downregulated isoforms of Fos. Unlike the acutely induced, short-lasting isoforms of Fos and FosB, the chronic Fras persist long after the last cocaine administration. The known form of delta FosB per se lacks the domain required to activate transcription. If the chronic Fras are similar in structure to delta FosB, then the induction of chronic Fras likely leads to a blockade of AP-1-dependent transcription resulting in altered gene expression. We presently purifying the chronic Fras to obtain amino acid sequence in order to directly examine our hypothesis about the effects of repeated cocaine administration on AP-1 dependent transcription and gene expression in the brain

Subjects by Vocabulary

Microsoft Academic Graph classification: AP-1 transcription factor Pharmacology Gene expression FOSB Activator (genetics) Neuroplasticity Psychology Nucleus accumbens Striatum Gene isoform

Subjects

History and Philosophy of Science, General Biochemistry, Genetics and Molecular Biology, General Neuroscience

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