Effects of dopamine and NMDA receptors on cocaine-induced Fos expression in the striatum of Fischer rats.
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.
Sun
Wei-Lun
WL
Department of Psychology, Hunter College, CUNY, 695 Park Ave, New York, NY 10065, USA. wsun@hunter.cuny.edu
Zhou
Luyi
L
Hazim
Ruhal
R
Quinones-Jenab
Vanya
V
Jenab
Shirzad
S
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
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