Effects of chronic treatment with (+)- and (-)-nicotine on nicotinic acetylcholine receptors and N-methyl-D-aspartate receptors in rat brain.
In this study, the effects of chronic treatment with (+)-nicotine on brain nicotinic acetylcholine receptors (nAChRs) and N-methyl-D-aspartate (NMDA) receptors, as well as on animal body weight were compared with those of chronic treatment with (-)-nicotine. Male Sprague-Dawley rats were s.c. injected with saline, (+)-nicotine (2.0 mg free base/kg b.w.) or (-)-nicotine (0.45 mg free base/kg b.w.) for 18 days. Brain nAChRs were investigated by (-)-[3H]nicotine binding. A significant increase in the high-affinity (-)-[3H]nicotine (5 nM)-binding sites was observed in the cortex, hippocampus, midbrain and striatum but not in the cerebellum of the rats treated with either (+)- or (-)-nicotine. The displacement curves of (-)-[3H]nicotine/(-)-nicotine in the cortices of rats treated with either (+)- or (-)-nicotine showed only one population of high-affinity binding sites, whereas both high- and low-affinity binding sites were observed in the cortices of control animals. Brain NMDA receptors were studied by [3H]MK-801, which binds to the NMDA receptor-ion channel complex. A significant decrease in the Bmax, but not in the KD for [3H]MK-801 binding in the cortices of rats treated with either (+)- or (-)-nicotine was only detected under certain experimental conditions where the NMDA receptors seem not to be maximally activated. The body weight of the animals treated with (-)-nicotine was significantly lower than that of the control animals, whereas there was no difference in body weight between (+)-nicotine- and saline-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Clinical Neurosciences and Family Medicine, Karolinska Institute, Huddinge University Hospital, Sweden.
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Zhang
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Gong
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Nordberg
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000378:metabolism; D008297:Male; D009538:Nicotine / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D013237:Stereoisomerism; D013997:Time Factors
D000596:Amino Acids; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic; D016291:Dizocilpine Maleate; D009538:Nicotine