Long‐Term Gene Expression in the Nucleus Accumbens Following Heroin Administration is Subregion‐Specific and Depends on the Nature of Drug Administration

Repeated exposure to addictive drugs results in long‐lasting neuroadaptations in the brain, especially in the mesocorticolimbic system. Within this system, the nucleus accumbens (NAc) plays a major integrative role. As such, the NAc has been shown to be a target of short‐ and long‐lasting drug‐induced neuroadaptations at the levels of neurotransmission and cellular morphology. The long‐lasting neuroadaptations might depend critically on alterations in gene expression. Recently, we obtained a set of transcripts by means of subtractive hybridization, of which the expression was decreased in the rat NAc shell after long‐term extinction of intravenous heroin self‐administration. Interestingly, the majority of these transcripts were also down‐regulated upon long‐term extinction of cocaine self‐administration. Using the yoked‐control operant paradigm, it was shown that non‐contingent administration of these drugs resulted in a totally different gene expression profile. However, in the rat NAc core, both self‐administration and non‐contingent heroin administration induced a qualitatively similar expression profile. Hence, cognitive processes associated with drug self‐administration seem to direct the long‐term genomic responses in the NAc shell, whereas the NAc core might primarily mediate the persistent pharmacological effects of addictive drugs (including Pavlovian conditioning).