Related Experiment Videos
Cocaine and the AP-1 Transcription Factor Complex.
1Molecular Plasticity Section (MPS), National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Building 36, Room 4C23, 36 Convent Drive, MSC-4135, Bethesda, Maryland 20892-4135, USA.
Annals of the New York Academy of Sciences
|November 2, 2017
Summary
Repeated cocaine use alters brain gene expression, leading to persistent addiction. Novel proteins called chronic Fos-related antigens (Fras) may block gene transcription, contributing to long-term neuroplasticity.
Area of Science:
- Neuroscience
- Molecular Biology
- Addiction Research
Background:
- Cocaine addiction persists long after drug clearance, indicating lasting neuroplasticity.
- Mechanisms of persistent cocaine-induced neuroplasticity remain unclear.
- Altered gene expression and brain signaling are implicated in addiction's long course.
Purpose of the Study:
- Investigate the molecular mechanisms of persistent cocaine addiction.
- Examine the role of gene expression changes in the striatum and nucleus accumbens.
- Test the hypothesis that novel Fos-related proteins mediate long-term effects.
Main Methods:
- Pretreatment of rats with repeated cocaine administrations.
- Acute cocaine challenge to assess immediate early gene (IEG) induction.
- Analysis of Fos and novel delta FosB-related proteins (chronic Fos-related antigens, Fras) in brain tissue.
- Purification of Fras for amino acid sequencing.
Main Results:
- Repeated cocaine downregulated immediate early gene induction by acute cocaine.
- Novel, persistent chronic Fos-related antigens (Fras) replaced downregulated Fos isoforms in the striatum and nucleus accumbens.
- Chronic Fras persist long after cocaine administration, unlike short-lasting Fos isoforms.
Conclusions:
- Repeated cocaine administration induces persistent changes in gene expression.
- Chronic Fras may block activator protein-1 (AP-1) dependent transcription.
- These alterations in gene expression likely contribute to the enduring nature of cocaine addiction.