Morphine induces c-fos and junB in striatum and nucleus accumbens via D1 and N-methyl-D-aspartate receptors.
Morphine induced the c-fos and junB immediate early genes in neurons of the medial and ventral striatum and nucleus accumbens. Induction of c-fos and junB mRNA and Fos protein was blocked by naloxone, the D1 dopamine (DA) receptor antagonists SCH23390 and SCH39166, and the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist MK801. SCH23390 attenuated morphine induction of AP-1 binding in striatum, suggesting that c-fos and junB contribute to AP-1 binding. SCH23390 and MK801 did not block morphine induction of c-fos and junB in septum. Since the morphine induction of c-fos and junB in striatum and nucleus accumbens (NA) was similar to that observed with cocaine and amphetamine, these data support current concepts that limbic striatum and NA are among the brain regions that mediate drug abuse. Furthermore, since DA and NMDA receptors may mediate opiate reward and opiate induction of c-fos and junB, the DA/NMDA regulation of c-fos and junB and their target genes may produce long-term changes in the striatal and NA circuits that contribute to opiate drug abuse.
Liu
J
J
Department of Neurology (V127), University of California at San Francisco 94121.
Nickolenko
J
J
Sharp
F R
FR
D000818:Animals; D001483:Base Sequence; D001552:Benzazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D017781:Genes, Immediate-Early; D016762:Genes, fos; D016758:Genes, jun; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009714:Nucleus Accumbens / Q000187:drug effects*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D015398:Signal Transduction
D001552:Benzazepines; D009838:Oligodeoxyribonucleotides; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate