Induction of c-fos immunostaining in the rat brain after the systemic administration of nicotine.
To search for evidence of altered neuronal gene expression in response to exposure to the highly addictive drug nicotine, rat brains were examined by immunocytochemistry for the fos protein after the systemic administration of nicotine. The drug was administered as an IV infusion over 1 h At a dose of 2 mg/kg, the most dramatic nicotine-induced fos nuclear immunostaining was seen in central visual pathways, including the superficial superior colliculus and the medial terminal nu. of the accessory optic tract, in the interpeduncular nu. Notably, many regions with high levels of nicotine binding sites, including the medial habenula, thalamus, substantia nigra, and ventral tegmental area, failed to express the c-fos gene with this schedule of nicotine administration. A minimal increase in fos immunostaining was seen after a nicotine dose of 0.5 mg/kg, with a much greater response after 1 or 2 mg/kg. The response was seen as soon as 60 min after the beginning of the infusion, was maximal at 2-3 h, and declined thereafter. c-fos expression was substantially attenuated in the superficial gray layer of superior colliculus, medial terminal nucleus of the accessory optic tract, and the interpeduncular nucleus by pretreatment with the centrally acting nicotine antagonist mecamylamine, 5 mg/kg IP, but not with the peripherally acting antagonist hexamethonium, 4 mg/kg IP. These observations identify a subset of central nervous system neurons that respond to nicotine with altered expression of the immediate early gene c-fos. These neurons presumably undergo long-term changes in gene expression as a result of acute exposure to high doses of nicotine.
Ren
T
T
Department of Neurology, University of California, San Francisco.
Sagar
S M
SM
D000818:Animals; D001921:Brain / Q000033:anatomy & histology* / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D003847:Deoxyglucose / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014795:Visual Pathways / Q000033:anatomy & histology / Q000187:drug effects
D016760:Proto-Oncogene Proteins c-fos; D009538:Nicotine; D003847:Deoxyglucose; D005947:Glucose