Long-term gene expression in the nucleus accumbens following heroin administration is subregion-specific and depends on the nature of drug administration

Edwin H Jacobs, August B. Smit, Taco J de Vries, Anton N M Schoffelmeer

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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).

Original languageEnglish
Pages (from-to)91-100
Number of pages10
JournalAddiction Biology
Issue number1
Publication statusPublished - Mar 2005

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