Cocaine and the AP‐1 Transcription Factor Complex

  title={Cocaine and the AP‐1 Transcription Factor Complex},
  author={Bruce T. Hope},
  journal={Annals of the New York Academy of Sciences},
  • B. Hope
  • Published 1 May 1998
  • Biology
  • Annals of the New York Academy of Sciences
ABSTRACT: Cocaine addiction 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 suggests the involvement of alterations in gene expression leading to altered signaling in… 
Chronic cocaine‐mediated changes in non‐human primate nucleus accumbens gene expression
CDNA hybridization arrays were used to illuminate cocaine‐regulated genes in the nucleus accumbens of non‐human primates, treated daily with escalating doses of cocaine over one year, finding adaptive responses coexist within a signaling scheme that could account for known inductions of genes.
Cocaine Up-Regulates Fra-2 and σ-1 Receptor Gene and Protein Expression in Brain Regions Involved in Addiction and Reward
The interaction between cocaine, fra-2, and σ-1 receptors involves brain regions that are established components of the neural circuit for reward, suggesting that they may contribute to the enduring changes that underlie the cellular basis of drug abuse.
Chronic wheel running affects cocaine-induced c-Fos expression in brain reward areas in rats
D1 dopamine receptor activation of NFAT‐mediated striatal gene expression
Findings reveal a novel molecular pathway that may contribute to the enduring modifications in striatal functioning that occur following the administration of drugs of abuse.
Ethanol-sensitive brain regions in rat and mouse: a cartographic review, using immediate early gene expression.
It is of interest that the amygdala, hippocampus, and prefrontal cortex, which belong to the reward system, are activated by cue-induced relapse to ethanol self-administration in rodents and humans, while activation of these regions is reversed with anti-craving compounds.
Glutathione peroxidase‐1 gene rescues cocaine‐induced conditioned place preference in mice by inhibiting σ‐1 receptor expression
The results suggest that GPx‐1 attenuates cocaine‐induced CPP via inhibition of σ‐1 receptor expression, indicating that the σ-1 receptor is a critical target for GPx-1‐mediated psychoprotective activity.
Ibogaine Signals Addiction Genes and Methamphetamine Alteration of Long‐Term Potentiation
It is reported that the actions of methamphetamine were similar to those of cocaine, including the propensity to alter long‐term potentiation (LTP) in the hippocampus of the rat brain, which suggests that there may be a “threshold” beyond which the excessive brain stimulation that probably occurs with compulsive psychostimulant use results in the occlusion of LTP.
Cocainomics: New Insights into the Molecular Basis of Cocaine Addiction
  • S. Hemby
  • Biology, Psychology
    Journal of Neuroimmune Pharmacology
  • 2009
The availability of gene and protein expression profiles will continue to expand the understanding of the short- and long-term consequences of drug addiction and other addictive disorders and may provide new approaches or new targets for pharmacotherapeutic intervention.


Regulation of immediate early gene expression and AP-1 binding in the rat nucleus accumbens by chronic cocaine.
The data suggest that chronic cocaine treatment leads to a persistent increase in AP-1 binding activity, which may be involved in some of the physiological and behavioral aspects of cocaine addiction.
Acute and chronic cocaine administration differentially alters striatal opioid and nuclear transcription factor mRNAs
Data indicate that repeated, high dose cocaine administration induces an increased PPD but not PPE genomic response and that the expression of c‐fos and zif/268 is dissociable from that of PPD.
Pharmacological studies of the regulation of chronic FOS-related antigen induction by cocaine in the striatum and nucleus accumbens.
An important role for dopaminergic neurotransmission in the induction of chronic Fras by cocaine is supported, which will assist in identifying the functional role played by these proteins in cocaine action.
FosB mutant mice: loss of chronic cocaine induction of Fos-related proteins and heightened sensitivity to cocaine's psychomotor and rewarding effects.
The finding that fosB mutant mice completely lacked basal levels of the 35- to 37-kDa Fos-related proteins demonstrates that a Fos family member protein plays a functional role in behavioral responses to drugs of abuse and implicates fos B gene products as important determinants of cocaine abuse.
Cocaine induces striatal c-fos-immunoreactive proteins via dopaminergic D1 receptors.
It is reported that the acute administration of a single dose of the indirect-acting dopaminergic agonist cocaine increases multiple Fos proteins in rat caudate nucleus and this data indicate that D1 dopamine receptors are linked to a cellular immediate-early gene system(s) and suggest an action of cocaine at one or more levels of gene expression via modulation of transcriptional processes in activated cells.
Cocaine-induced c-fos messenger RNA is inversely related to dynorphin expression in striatum
  • H. Steiner, C. Gerfen
  • Biology
    The Journal of neuroscience : the official journal of the Society for Neuroscience
  • 1993
The results suggest that the restricted regional pattern of cocaine-induced c-fos expression is related, in part, to the basal level of dynorphin expression, and that cocaine treatment elevates dynorphIn expression in striatal regions with a strong c-Fos response, thereby limiting subsequent c- fos induction by cocaine.
Regulation of delta FosB and FosB-like proteins by electroconvulsive seizure and cocaine treatments.
It is shown that delta FosB, a truncated splice variant of FsB, responds like the other acute Fras: it is induced rapidly and transiently in cerebral cortex after acute electroconvulsive seizure (ECS) and in striatum after acute cocaine but does not accumulate after chronic ECS or cocaine treatment.
Chronic electroconvulsive seizure (ECS) treatment results in expression of a long-lasting AP-1 complex in brain with altered composition and characteristics
The altered composition of the chronic AP-1 complex, and differences in half-life, DNA binding affinity, and possibly transcriptional activating properties are likely to cause changes in the overall pattern of gene expression, which may underlie some of the long-term biochemical adaptations observed following chronic ECS and other chronic perturbations.