title: The effects of D1 or D2 dopamine receptor blockade on zif/268 and preprodynorphin gene expression in rat forebrain following a short-term cocaine binge.
abstract: Selective D1 or D2 dopamine receptor antagonists were used to investigate the transynaptic regulation of mRNAs coding for the opioid peptide, preprodynorphin, and the nuclear transcription factor, zif/268 after an acute cocaine binge. Rats were injected intraperitoneally with the D1 receptor antagonist, SCH 23390, or the D2 receptor antagonist, sulpiride, 30 min prior to 3 hourly injections of saline or 20 mg/kg cocaine and killed 1 h after the final injection. Behavioral ratings indicated that SCH 23390 blocked, whereas sulpiride augmented, cocaine-induced stereotypical behaviors. Striatal sections were hybridized with oligonucleotides coding for zif/268 and preprodynorphin. Quantitative image analysis of autoradiograms revealed that (1) SCH 23390 completely suppressed basal and cocaine binge-induced zif/268 mRNA in the striatal and cerebral cortical areas examined; (2) sulpiride enhanced basal levels of zif/268 mRNA in the medial caudate and dorsomedial shell of the nucleus accumbens; (3) sulpiride partially blocked cocaine binge-induced levels of zif/268 mRNA in the dorsal striatum but had no effect in sensory cortex; (4) SCH 23390, but not sulpiride, significantly reduced the constitutive expression of preprodynorphin mRNA; and (5) SCH 23390 and sulpiride blocked cocaine binge-induced expression of preprodynorphin mRNA in the dorsal striatum.
authors.affiliation: Department of Anatomy and Cell Biology, East Carolina University School of Medicine, Greenville 27858-4354, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Daunais
authors.forename: J F
authors.initials: JF
authors.lastname: McGinty
mesh_terms: D000818:Animals; D001345:Autoradiography; D001552:Benzazepines / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004399:Dynorphins / Q000096:biosynthesis*; D051766:Early Growth Response Protein 1; D015870:Gene Expression / Q000187:drug effects; D017874:Immediate-Early Proteins; D017403:In Situ Hybridization; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism; D009928:Organ Specificity; D016548:Prosencephalon / Q000187:drug effects* / Q000378:metabolism*; D011498:Protein Precursors / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000502:physiology; D013239:Stereotyped Behavior / Q000187:drug effects; D013462:Sulfur Radioisotopes; D013469:Sulpiride / Q000494:pharmacology; D013569:Synapses / Q000502:physiology; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis*; D016335:Zinc Fingers
chemical_list: D001552:Benzazepines; D004268:DNA-Binding Proteins; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013462:Sulfur Radioisotopes; D014157:Transcription Factors; C036448:pre-prodynorphin; D004399:Dynorphins; D013469:Sulpiride; D003042:Cocaine