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

AbstractRepeated exposure to addictive drugs results in long-lasting neuroadaptations in the brain, especiallyin the mesocorticolimbic system. Within this system, the nucleus accumbens (NAc) plays a majorintegrative 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-lastingneuroadaptations might depend critically on alterations in gene expression. Recently, we obtained a setof transcripts by means of subtractive hybridization, of which the expression was decreased in the ratNAc shell after long-term extinction of intravenous heroin self-administration. Interestingly, themajority 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-contingentadministration of these drugs resulted in a totally different gene expression profile. However, in the ratNAc core, both self-administration and non-contingent heroin administration induced a qualitativelysimilar expression profile. Hence, cognitive processes associated with drug self-administration seem todirect the long-term genomic responses in the NAc shell, whereas the NAc core might primarilymediate the persistent pharmacological effects of addictive drugs (including Pavlovian conditioning).

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