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).
Jacobs
Edwin H
EH
Department of Medical Pharmacology, Research Institute Neurosciences, VU Medical Center, Vrije Universiteit, Amsterdam, the Netherlands. e.jacobs@erasmusmc.nl
Smit
August B
AB
de Vries
Taco J
TJ
Schoffelmeer
Anton N M
AN
D000222:Adaptation, Physiological; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004333:Drug Administration Routes; D015870:Gene Expression / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D003932:Heroin / Q000008:administration & dosage / Q000494:pharmacology*; D006556:Heroin Dependence / Q000503:physiopathology; D006801:Humans; D006824:Hybridization, Genetic; D009419:Nerve Tissue Proteins / Q000187:drug effects* / Q000235:genetics*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors
D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; D003932:Heroin