Persistent alterations in mesolimbic gene expression with abstinence from cocaine self-administration

Area of Science:

• Neuroscience
• Molecular Biology
• Addiction Research

Background:

• Cocaine-induced gene expression changes are known after short abstinence periods.
• Limited data exist on the persistence of these changes after long-term abstinence.

Purpose of the Study:

• To investigate extinction responding, gene expression, and chromatin remodeling after long-term cocaine abstinence.
• To examine the persistence of cocaine-responsive gene expression changes in the medial prefrontal cortex (mPFC) and nucleus accumbens.

Main Methods:

• Rats underwent discrete-trial cocaine self-administration followed by prolonged forced abstinence (30 and 100 days).
• Extinction responding, mRNA abundance of cocaine-responsive genes (c-fos, Nr4a1, Arc, EGR1, CART, NPY), and histone H3 acetylation were measured.

Main Results:

• Extinction responding increased with longer abstinence periods (30 and 100 days).
• mRNA levels of c-fos, Nr4a1, Arc, and EGR1 decreased and persisted in the mPFC and nucleus accumbens.
• Histone H3 acetylation changes were observed at the promoters of EGR1 and NPY in the mPFC.

Conclusions:

• Prolonged cocaine abstinence leads to persistent changes in gene expression and behavior, suggesting enduring neurobiological adaptations.
• Chromatin remodeling may play a regulatory role in these persistent molecular changes following cocaine self-administration.