EFFECT OF SMOKING HISTORY ON [H-3] NICOTINE BINDING IN HUMAN POSTMORTEM BRAIN

Chronic nicotine administration in animal models evokes a dose-depende nt increase in brain nicotinic receptor numbers. Genetically determine d variability in nicotinic receptor number in different mouse strains has also been reported, which is thought to affect sensitivity to nico tine, as well as the development of tolerance. Humans self-administer nicotine principally in the form of cigarettes and other tobacco produ cts. The present study compared [H-3]nicotine binding in human postmor tem brain from thalamus and hippocampus of nonsmoking subjects, subjec ts who had variable life-long smoking histories and subjects who had q uit smoking. A significant increase was seen in [H-3]nicotine binding in both hippocampus and thalamus of subjects with life-long smoking hi stories. In the hippocampus, this change resulted from a change in tot al receptor number (B-max), with no change in receptor affinity (K-d). There was also a positive correlation between the degree of smoking, as measured by the average reported packs smoked per day, and the numb er of nicotine binding sites found in both the hippocampus and thalamu s, showing that humans exhibit a dose-dependent increase in brain nico tinic receptor binding. Receptor levels in these brain regions after s moking cessation were at or below those found in the control populatio n, which indicated that smoking-induced changes are reversible after c essation of nicotine treatment. These results suggest that increases i n nicotinic receptor levels in the human brain may underlie nicotine t olerance and addiction in smokers.