Nicotine-induced fos expression in the pedunculopontine mesencephalic tegmentum in the rat.
The aim of this study was to assess the effects of a single dose of nicotine (NIC, 0.3 or 1.0 mg/kg, s.c.), after survival times of 30, 60 or 120 min, on immediate early gene expression in the pedunculopontine mesencephalic tegmentum (PMT), using Fos-immunocytochemistry. Either doses of NIC strongly increased Fos-immunoreactivity in both the pedunculopontine tegmental nucleus (PPTg) and the laterodorsal tegmental nucleus (LDTg), as compared to the saline controls, at 30 min and 60 min. In comparison, the effects of NIC-induced Fos expression in the caudate-putamen (CP) were not as strong as the ones observed in the PPTg and LDTg. In fact, at 30 min the 0.3 mg/kg dose of NIC did not induce Fos-expression, unlike the PPTg and LDTg. The CP response was more noticeable in the mediodorsal than in the laterodorsal region. Double-labelling studies using Fos-immunoreactivity and NADPH-diaphorase histochemistry for cholinergic cells in the PPTg and LDTg revealed that, in general, cholinergic neurons had Fos negative nuclei, although double-labelled neurons were occasionally seen in the PPTg. In conclusion, systemically administered NIC activates the neuronal population of the PPTg and the LDTg possibly by directly targeting nicotinic receptors that may be located in non-cholinergic neurons. We postulate that activation of these non-cholinergic neurons modulates the activity of cholinergic cells in the PMT, which in turn may alter dopamine release in the mesolimbic system.
José Lança
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A
Centre for Addiction and Mental Health, University of Toronto, Ontario, M5S 2S1, Toronto, Canada. aj.lanca@utoronto.ca
Sanelli
T R
TR
Corrigall
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WA
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009538:Nicotine / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000633:toxicity*; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D011149:Pons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D013681:Tegmentum Mesencephali / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D018722:Nicotinic Agonists; D009538:Nicotine; D009252:NADPH Dehydrogenase