Smoking and mental health - NCSCT

3
Neurobiological and behavioural
mechanisms linking smoking and mental
disorders
Although the prevalence of smoking among people with mental disorders is
high, and as outlined in Chapter 2 has proved relatively refractory to change, the
mechanisms underlying this association, and in particular the direction of
causation between smoking and mental illness, remain poorly understood. This
chapter reviews some of the biological mechanisms that may be responsible for
the association between smoking and mental disorders.
3.1 Mechanisms of nicotine addiction
There is widespread agreement that nicotine is the principal addictive
component of tobacco smoke. Behavioural studies with experimental animals
have provided convincing evidence that nicotine has the behavioural properties
of drugs of dependence, because nicotine serves as a reinforcer in selfadministration
studies, 1,2 and abrupt withdrawal after a period of continuous
infusion evokes a withdrawal syndrome, which is reversed by the readministration
of nicotine. 3,4 The behavioural changes evoked by nicotine
withdrawal in this paradigm are thought to model important components of the
abstinence syndrome experienced by many smokers when they first quit
smoking. 5,6 Neurobiological studies have also shown that nicotine acts on neural
pathways within the brain that have been implicated in reward and
reinforcement. In experimental animals, injections of nicotine delivered noncontingently
(ie by an experimenter) or contingently (by self-administration)
stimulate the release of dopamine in both the shell and core subdivisions of the
nucleus accumbens. 7–9 Repeated daily administration of the drug results in
sensitisation of its effects on dopamine (DA) overflow in the core subdivision of
the accumbens. 10–12 This effect is independent of contingency. However, repeated
self-administration of nicotine across days also results in sensitisation of its effect
on DA overflow in the shell subdivision of the accumbens. 9 Sensitisation of these
pathways is a property of drugs of dependence of different pharmacological
groups, and has been implicated in the transition from simple reinforcement to
the compulsive drug-seeking and drug-taking behaviour that characterises
dependence. 13,14
38 © Royal College of Physicians 2013