Toggle Main Menu Toggle Search

Open Access padlockePrints

Dopamine and nicotinic receptor binding and the levels of dopamine and homovanillic acid in human brain related to tobacco use

Lookup NU author(s): Dr Jennifer Court, Stephen Lloyd, Dr Margaret Piggott, Dr Christopher Morris, Emeritus Professor Robert Perry, Emeritus Professor Elaine Perry

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

Reports of a reduction in the risk of developing Parkinson's disease and Alzheimer's disease in tobacco smokers, together with the loss of high- affinity nicotine binding in these diseases, suggest that consequences of nicotinic cholinergic transmission may be neuroprotective. Changes in brain dopaminergic parameters and nicotinic receptors in response to tobacco smoking have been assessed in this study of autopsy samples 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 compared with age matched non- smokers (P<0.05) in both the caudate and putamen. Dopamine levels were significantly elevated in the caudate of smokers compared with non-smokers (P<0.05). However there was no significant change in the numbers of dopamine (D1, D2 and D3) receptors or the dopamine transporter in the striatum, or for dopamine D1 and D2 receptors in the hippocampus in smokers compared with non- smokers or ex-smokers. The density of high-affinity nicotine binding was higher in smokers than non-smokers in the hippocampus, entorhinal cortex and cerebellum (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 similar to that of the non-smokers in all the areas investigated. The differences in high-affinity nicotine binding between smokers and the non- and ex-smokers could not be explained by variation in apolipoprotein E genotype. There were no differences in α-bungarotoxin binding, measured in hippocampus and cerebellum, between any of the groups. These findings suggest that chronic cigarette smoking is associated with a reduction of the firing of nigrostriatal dopaminergic neurons in the absence of changes in the numbers of dopamine receptors and the dopamine transporter. Reduced dopamine turnover associated with increased numbers of high-affinity nicotine receptors is consistent with attentuated efficacy of these receptors in smokers. A decrease in striatal dopamine turnover may be a mechanism of neuroprotection in tobacco smokers that could delay basal ganglia pathology. The current findings are also important in the interpretation of measurements of nicotinic receptors and dopaminergic parameters in psychiatric conditions such as schizophrenia, in which there is a high prevalence of cigarette smoking.


Publication metadata

Author(s): Piggott MA; Perry RH; Perry EK; Morris CM; Lloyd S; Court JA; Thomas N; Marshall EF; Lamb H; Johnson M

Publication type: Article

Publication status: Published

Journal: Neuroscience

Year: 1998

Volume: 87

Issue: 1

Pages: 63-78

Print publication date: 30/06/1998

ISSN (print): 0306-4522

ISSN (electronic): 1873-7544

Publisher: Pergamon Press

URL: http://dx.doi.org/10.1016/S0306-4522(98)00088-8

DOI: 10.1016/S0306-4522(98)00088-8

PubMed id: 9722142


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share