D1 dopamine receptor-deficient mouse: cocaine-induced regulation of immediate-early gene and substance P expression in the striatum.
Psychomotor stimulants such as cocaine alter gene expression in neurons of the striatum. Whereas many of these effects are mediated by D1 dopamine receptors, the involvement of other dopamine receptor subtypes or neurotransmitters is likely. To distinguish between these possibilities, regulation by cocaine of immediate-early genes and genes encoding neuropeptides was analysed in mice that lack functional D1 receptors. Gene expression was examined with in situ hybridization histochemistry. In these animals, cocaine failed to induce the immediate-early genes c-fos and zif 268. In contrast, substance P expression was abnormally increased by this drug. These results demonstrate that some of the effects of cocaine on gene regulation are mediated via D1 receptor-dependent mechanisms, as evidenced by the absence of immediate-early gene induction in D1-deficient mice, whereas others also involve additional, non-D1 receptor mechanisms, as shown for substance P expression.
Drago
J
J
Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.
Gerfen
C R
CR
Westphal
H
H
Steiner
H
H
D000818:Animals; D001483:Base Sequence; D001835:Body Weight; D001921:Brain / Q000033:anatomy & histology / Q000502:physiology*; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004399:Dynorphins / Q000096:biosynthesis; D051766:Early Growth Response Protein 1; D004745:Enkephalins / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects*; D017781:Genes, Immediate-Early / Q000187:drug effects; D006579:Heterozygote; D006720:Homozygote; D017874:Immediate-Early Proteins; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D009929:Organ Size; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D017447:Receptors, Dopamine D1 / Q000172:deficiency* / Q000235:genetics*; D013373:Substance P / Q000096:biosynthesis*; D014157:Transcription Factors / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D004745:Enkephalins; D017874:Immediate-Early Proteins; D015345:Oligonucleotide Probes; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D014157:Transcription Factors; D013373:Substance P; D004399:Dynorphins; D003042:Cocaine