Active heroin administration induces specific genomic responses in the nucleus accumbens shell

SPECIFIC AIMIn view of possible context-dependent factors in drug-induced neuroplasticity, the objective of this study was to compare the genomic response in the rat nucleus accumbens (NAc) shell after long-term withdrawal of active and passive heroin administration. To identify differentially regulated transcripts in the NAc shell after long-term extinction of heroin self-administration (SA), we constructed a subtraction library and preselected a set of transcripts of which expression was assessed in different cohorts of rats with a history of heroin or cocaine exposure (SA and forced administration; FA) by means of real-time quantitative PCR. We found that active drug consumption during SA (instrumental learning) is a crucial psychological factor directing long-term genomic consequences in the brain.PRINCIPAL FINDINGS1. Construction of the subtraction libraryRats were trained using a widely employed heroin self-administration paradigm. After 18 daily sessions of extinction of SA behavior, we constructed...