Involvement of nitric oxide in morphine-induced c-Fos expression in the rat striatum.
Induction of expression of immediate-early gene c-Fos in the striatum is a common effect of many drugs of abuse, including morphine. Previous studies have shown that the morphine-mediated c-Fos response is attenuated by antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Other evidence suggests that the NDMA receptor may be coupled to the enzyme neuronal nitric oxide synthase (nNOS). NMDA receptor-mediated increases in intracellular calcium can activate nNOS, which catalyzes the formation of the signaling molecule nitric oxide. Because activation of NMDA receptors mediates morphine-induced c-Fos expression, we tested the hypothesis that activation of nNOS is involved in this cascade. Male rats were injected with the nNOS-selective inhibitor 7-nitroindazole (7-NI) or vehicle 30 min prior to injection of morphine sulfate or vehicle. Two hours later they were perfused with fixative and the brains removed for immunocytochemical analysis for c-Fos. Morphine induced c-Fos expression in the striatum, cerebral cortex, and midline/intralaminar nuclei of thalamus. Expression in the striatum, but not thalamus or cortex, was significantly blocked by 7-NI. Double-label immunocytochemistry revealed no co-localization of c-Fos and nNOS in any brain region. These results support a role for nNOS in the neural circuits activated by morphine.
Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, LA 70112, USA. harlanre@tulane.edu
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Harlan
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Webber
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Garcia
D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016762:Genes, fos / Q000187:drug effects* / Q000502:physiology; D007191:Indazoles / Q000494:pharmacology; D007395:Interneurons / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000187:drug effects* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism
D004791:Enzyme Inhibitors; D007191:Indazoles; D009294:Narcotics; D016194:Receptors, N-Methyl-D-Aspartate; D009020:Morphine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; C080122:7-nitroindazole