title: Effects of dopamine and NMDA receptors on cocaine-induced Fos expression in the striatum of Fischer rats.
abstract: Cocaine is an addictive psychostimulant that induces immediate early gene (IEG) expression by activating dopamine (DA) D1 and glutamate NMDA receptors in the striatum. In this study, we show that a single cocaine administration (30 mg/kg) time-dependently increases ERK phosphorylation, c-Fos and FosB protein expression, and MKP-1 phosphorylation (p-MKP-1), in the caudate-putamen (CPu) and nucleus accumbens (NAc) of Fischer rats. In the CPu, 1 h after cocaine injection, the increase in c-Fos and FosB protein expressions is totally abolished by pre-administration of DA-D1 receptor antagonist, SCH23390. In the NAc, SCH23390 also inhibits cocaine-induced c-Fos protein expression. The pre-treatment of NMDA receptor antagonist, MK801, partially reduces cocaine-activated c-Fos protein expression in the CPu. Furthermore, the escalation of p-MKP-1 after acute cocaine administration is dependent on both DA-D1 and NMDA receptor activation in both brain regions examined. Our data suggest that cocaine may modulate ERK pathway signaling through the activation of DA-D1 and NMDA receptors, subsequently influencing the IEG protein expression.
authors.affiliation: Department of Psychology, Hunter College, CUNY, 695 Park Ave, New York, NY 10065, USA. wsun@hunter.cuny.edu
authors.forename: Wei-Lun
authors.initials: WL
authors.lastname: Sun
authors.forename: Luyi
authors.initials: L
authors.lastname: Zhou
authors.forename: Ruhal
authors.initials: R
authors.lastname: Hazim
authors.forename: Vanya
authors.initials: V
authors.lastname: Quinones-Jenab
authors.forename: Shirzad
authors.initials: S
authors.lastname: Jenab
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D054638:Dual Specificity Phosphatase 1 / Q000187:drug effects / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D017781:Genes, Immediate-Early / Q000187:drug effects / Q000235:genetics; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; C483820:Fosb protein, rat; D016760:Proto-Oncogene Proteins c-fos; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D048049:Extracellular Signal-Regulated MAP Kinases; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat; D003042:Cocaine; D004298:Dopamine