DOPAMINE AND NICOTINIC RECEPTOR-BINDING AND THE LEVELS OF DOPAMINE AND HOMOVANILLIC-ACID IN HUMAN BRAIN RELATED TO TOBACCO USE

Reports of a reduction in the risk of developing Parkinson's disease a nd Alzheimer's disease in tobacco smokers, together with the loss of h igh-affinity nicotine binding in these diseases, suggest that conseque nces of nicotinic cholinergic transmission may be neuroprotective, Cha nges in brain dopaminergic parameters and nicotinic receptors in respo nse to tobacco smoking have been assessed in this study of autopsy sam ples from normal elderly individuals with known smoking histories and apolipoprotein E genotype. The ratio of homovanillic acid to dopamine, an index of dopamine turnover, was reduced in elderly smokers compare d with age matched non-smokers (P<0.05) in both the caudate and putame n. Dopamine levels were significantly elevated in the caudate of smoke rs compared with non-smokers (P<0.05). However there was no significan t change in the numbers of dopamine (D1, D2, and D3) receptors or the dopamine transporter in the striatum, or for dopamine D1 and D2 recept ors in the hippocampus in smokers compared with non-smokers or ex-smok ers. The density of high-affinity nicotine binding was higher in smoke rs than non-smokers in the hippocampus, entorhinal cortex and cerebell um (elevated by 51-221%) and to a lesser extent in the striatum (25-55 %). The density of high-affinity nicotine binding in ex-smokers was si milar to that of the non-smokers in all the areas investigated. The di fferences in high-affinity nicotine binding between smokers and the no n- and ex-smokers could not be explained by variation in apolipoprotei n E genotype. There were no differences in alpha-bungarotoxin binding, measured in hippocampus and cerebellum, between any of the groups. Th ese findings suggest that chronic cigarette smoking is associated with a reduction of the firing of nigrostriatal dopaminergic neurons in th e absence of changes in the numbers of dopamine receptors and the dopa mine transporter. Reduced dopamine turnover associated with increased numbers of high-affinity nicotine receptors is consistent with attentu ated efficacy of these receptors in smokers. A decrease in striatal do pamine turnover may be a mechanism of neuroprotection in tobacco smoke rs that could delay basal ganglia pathology. The current findings are also important in the interpretation of measurements of nicotinic rece ptors and dopaminergic parameters in psychiatric conditions such as sc hizophrenia, in which there is a high prevalence of cigarette smoking. (C) 1998 IBRO. Published by Elsevier Science Ltd.