Hypothesis: a nicotine-dopamine interaction linking smoking with Parkinson's disease and tardive dyskinesia.
1. Nicotine, an important pharmacological component of cigarette smoke, is known to have significant effects on central nervous system (CNS) dopaminergic function. Although acute doses of nicotine have been shown to facilitate dopamine release, recent data indicate that chronic nicotine treatment may actually decrease CNS dopamine turnover in the striatum. 2. A number of epidemiological investigations have demonstrated that individuals who are or who have been smokers are less likely to develop idiopathic Parkinson's disease (a disorder involving a deficit in nigrostriatal dopaminergic neurotransmission). In addition, there is preliminary evidence that individuals with tardive dyskinesia (a hyperkinetic movement disorder observed in some cases of chronic neuroleptic treatment and thought by some to be associated with striatal dopamine receptor supersensitivity) are more likely to be smokers. 3. A unitary hypothesis is presented, proposing that smoking in early adult life may decrease CNS catecholamine turnover, thereby protecting against free radical formation from catecholamine oxidation that in turn damages striatal neurons. These individuals are thereby "protected" from the later development of Parkinson's disease. In this hypothetical scheme, individuals who are given neuroleptics and who also are smokers may develop a greater degree of dopamine receptor supersensitivity due to combined receptor blockade by neuroleptics and a decrease in CNS dopamine turnover caused by nicotine, resulting in an increased prevalence of tardive dyskinesia in this group.
Kirch
D G
DG
Neuropsychiatry Branch, National Institute of Mental Health, Washington, D.C. 20032.
Alho
A M
AM
Wyatt
R J
RJ
D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D009538:Nicotine / Q000378:metabolism*; D010302:Parkinson Disease, Secondary / Q000209:etiology / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism*
D009538:Nicotine; D004298:Dopamine