EFFECTS OF CHRONIC TREATMENT WITH (+)-NICOTINE 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 these 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(-)-[H-3]nicotine binding. A significant increase in the high-affinity(-)-[H-3]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 (-)-[H-3]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 [H-3]MK-801, which binds to the NMDA receptor-ion channel complex. A significant decrease in the B-max, but not in the K-D for [H-3]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. These results show that (+)-nicotine treatment has an effect on nAChRs in rat brains which is similar to that of(-)-nicotine treatment, but an effect on body weight which differs from (-)-nicotine, and also suggest that nicotinic agonists may interact with brain NMDA receptors in vivo.