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Vol. 289, Issue 3, 1545-1552, June 1999
Department of Pharmacology, The George Washington University
Medical Center, Washington, DC (D.C.P.); Department of Pharmacology,
Georgetown University School of Medicine, Washington, DC (M.I.D-G.,
K.J.K.); and Department of Psychiatry, Case Western Reserve University
School of Medicine, Cleveland, Ohio (C.A.S.)
Chronic administration of nicotine increases the density of neuronal
cholinergic nicotinic receptors in cells and in rodent brain, and
similar increases have been reported in brains from human smokers. To
further examine this phenomenon, we measured nicotinic receptor binding
sites in brain regions from matched populations of smokers and
nonsmokers. We first measured binding of
[3H](±)epibatidine ([3H]EB) and
[3H]cytisine in homogenate preparations from samples of
prefrontal and temporal cerebral cortex. Binding of each radioligand
was significantly higher (250-300%) in both cortical regions from brains of smokers. Frozen sections from each of the cerebral cortical regions and the hippocampus were used for autoradiographic analysis of
[3H]EB binding. In cerebral cortex, binding was most
dense in layer VI in the prefrontal cortex and layers IV and VI in the
temporal cortex. Densitometric analysis of [3H]EB binding
sites revealed marked increases of 300 to 400% of control in all
cortical regions examined from smokers' brains. Binding in the
hippocampal formation was heterogeneously distributed, with dense areas
of binding sites seen in the parasubiculum, subiculum, and molecular
layer of the dentate gyrus, and the lacunosum-moleculare layer of the
CA1/2. Binding of [3H]EB was significantly higher
in all six regions of the hippocampus examined from brains of smokers
compared with nonsmokers. These increases ranged from 160% of control
in parasubiculum to 290% in the molecular layer of the dentate gyrus.
The increase in nicotinic receptors in the cerebral cortex and
hippocampus of smokers may modify the central nervous system effects of
nicotine and contribute to an altered response of smokers to nicotine.
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