| Vol 7 n°3 - Pharmacology
in mood disorders |
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he observation that a large majority of psychi-
atric patients smoke cigarettes leads to the question
about the possible relationship between smoking, depen-
dence, and neurological diseases. 1,2 Several
studies have
reported an association between smoking and depres-
sion. 3,4 This question takes
on a new dimension when we
consider that nicotine, the natural alkaloid contained in
tobacco leaves, is a powerful and addictive compound
acting on the central nervous system (CNS).
A pivotal point in this line of thinking is what we know
about the mechanisms by which nicotine acts on the CNS
and what we can gain from a better understanding of the
intimate processes that drive to tobacco consumption.5,6
In this article, we will examine the basic functioning of
the key players in nicotine addiction, ie, the neuronal
nicotinic acetylcholine (ACh) receptors, and their possi-
ble role in depression.
First called Vagustoff by
Loewi, due to its discovery in the
heart muscle in 1921, the neurotransmitter ACh exerts
many different actions.ACh is synthesized in the terminal
bouton and stored in clear vesicles, and is released by
nerve activity in the synaptic cleft.After a rapid increase,
the ACh concentration quickly declines due to rapid
hydrolysis (catalyzed by the enzyme acetylcholinesterase)
and diffusion.The determinant role of this enzymatic activ-
ity in regulating the cholinergic tone and its brain function
was revealed more than 150 years ago, well before the dis-
covery of ACh, with the use of compounds that were later
shown to be centrally active anticholinesterase agents.7,8
B a s i c r e s e a r c h
Copyright © 2005 LLS SAS. All rights reserved
The possible contribution of neuronal
nicotinic acetylcholine receptors in
Keywords:
nicotine; depression; ligand-gated channel; acetylcholine
Author affiliations: Department of Neuroscience,
Medical Faculty,
Geneva University Hospitals, Geneva, Switzerland
Address for correspondence: Department of Neuroscience,
Medical Faculty,
Geneva University Hospitals, CMU, 1, rue Michel Servet, CH-1211 Geneva 4,
(e-mail: daniel.bertrand@medecine.unige.ch)
Although tobacco use and smoking were introduced
long ago, it was only recently that the nicotine con-
tained in the tobacco leaves was recognized as an addic-
tive substance acting on the central nervous system
(CNS). However, even prior to this recognition, several
studies have reported an association between smoking
and psychiatric disorders. One of the many observations
was that smoking cessation is accompanied by a marked
increase in the probability of major depression. In par-
allel with the discovery of the neuronal nicotinic acetyl-
choline receptors and their extensive expression in the
CNS, this association sheds new light on the influence of
cholinergic transmission in depression. In this article, we
examine the various modes of action of nicotine in the
CNS and discuss the mechanisms by which this alkaloid
can prevent or precipitate mood disorders, and the pos-
sibility of discovering new therapeutic avenues for the
Dialogues Clin Neurosci. 2005;7:207-216.
