Abstract
Chronic nicotine administration in animal models evokes a dose-dependent increase in brain nicotinic receptor numbers. Genetically determined variability in nicotinic receptor number in different mouse strains has also been reported, which is thought to affect sensitivity to nicotine, as well as the development of tolerance. Humans self-administer nicotine principally in the form of cigarettes and other tobacco products. The present study compared [3H]nicotine binding in human postmortem brain from thalamus and hippocampus of nonsmoking subjects, subjects who had variable life-long smoking histories and subjects who had quit smoking. A significant increase was seen in [3H]nicotine binding in both hippocampus and thalamus of subjects with life-long smoking histories. In the hippocampus, this change resulted from a change in total 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 number of nicotine binding sites found in both the hippocampus and thalamus, showing that humans exhibit a dose-dependent increase in brain nicotinic receptor binding. Receptor levels in these brain regions after smoking cessation were at or below those found in the control population, which indicated that smoking-induced changes are reversible after cessation of nicotine treatment. These results suggest that increases in nicotinic receptor levels in the human brain may underlie nicotine tolerance and addiction in smokers.
Footnotes
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Send reprint requests to: Dr. Sherry Leonard, Department of Psychiatry, Box C268–71, University of Colorado Health Sciences Center, 4200 E. 9th Avenue, Denver, CO 80262.
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↵1 This work was supported by USPHS Grants, DA09457 and VA Medical Research Service to S.L., DA03194 and DA00197 to A.C.C. and AA11164 to C.R.B.
- Abbreviations:
- αBTX
- α-bungarotoxin
- HEPES
- N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid
- PMI
- postmortem interval
- Received October 15, 1996.
- Accepted March 6, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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