Time and brain region specific up-regulation of low affinity neuronal nicotinic receptors during chronic nicotine administration in mice

We studied the effects of chronic oral nicotine on brain low affinity nicotine binding sites. Mice received nicotine in the drinking water for 4 or 7 weeks. Receptor binding was measured at 24 or 48 It after cessation of nicotine administration with [H-3]methyllycaconitine, an antagonist in alpha 7 and alpha 3/alpha 6 beta 2 beta 3 nicotinic receptors in striatium, midbrain, hippocampus and cortex. Chronic nicotine for 4 weeks resulted in a significant increase in the [H-3]methyllycaconitine binding in the striatum and cortex, whereas after 7 weeks the increase in binding could be found in the hippocampus but not in the other brain areas studied. For comparison, high affinity nicotine binding sites (mostly alpha 4 beta 2) were measured with [H-3] epibatidine after 7-week chronic nicotine treatment. [H-3]Epibatidine binding sites were increased in the hippocampus, midbrain and cortex, but not in the striatum. The up-regulation of [H-3]methyllycaconitine binding was significant at 24 h but that of [H-3]epibatidine binding sites was not observed until at 48 h after cessation of chronic nicotine. These results suggest that up-regulation of low affinity nicotine binding sites does occur during chronic nicotine administration. Furthermore, the low affinity and high affinity binding differ clearly as regards regions and duration suggesting that different nicotinic receptors respond differently to nicotine administration. (c) 2005 Elsevier B.V. All rights reserved.