CHAPTER 7
Tobacco Dependence
GARY E. SWAN, KAREN S. HUDMON, AND TALINE V. KHROYAN
147
BASIC MECHANISMS OF NICOTINE ADDICTION 148
ANIMAL MODELS OF NICOTINE ADDICTION 149
Self-Administration 149
The Place-Conditioning Paradigm 151
Preclinical Genetic Models: Insights into Individual
Differences in Nicotine-Induced Behavior 152
Relevance of Preclinical Studies to Understanding
Tobacco Dependence 152
SOCIAL AND PSYCHOLOGICAL RISK FACTORS
FOR INITIATION AND MAINTENANCE OF
TOBACCO USE 153
Gender and Ethnic Differences 153
Cognitive Effects of Smoking 153
Psychiatric Comorbidity and Tobacco Dependence 153
ENVIRONMENTAL RISK FACTORS FOR INITIATION 154
Tobacco Advertising and Promotions 154
Effects of Pricing and Tobacco Control Policies 154
Youth Access to Tobacco 155
PREVENTION AND TREATMENT OF
TOBACCO DEPENDENCE 155
Cessation Methods 155
EVIDENCE FOR GENETIC INFLUENCE ON TOBACCO USE
IN HUMANS 157
Definition of Phenotypes 158
Evidence for a Genetic Basis to a Variety of
Smoking-Related Phenotypes 158
Tobacco Dependence: A Construct in
Need of Refinement 159
The Potential Importance of Gene-Behavior-Environment
Interactions in Tobacco Dependence 160
PUBLIC HEALTH IMPERATIVE FOR COLLABORATIVE,
TRANSDISCIPLINARY RESEARCH 160
Ethical Considerations 161
SUMMARY 161
REFERENCES 162
Tobacco dependence is determined by psychosocial, envi-
ronmental, and biological factors. Individual differences in
exposure to various environmental risk factors in”uence sus-
ceptibility to become addicted to nicotine initially just as do
differences in a multitude of biological and physiological
characteristics. Moreover, the extent to which the various risk
factors interact with each other within and across these broad
sources of individual variation provide additional sources of
in”uence that can determine an individual•s likelihood of
becoming addicted to nicotine once exposed. Smoking be-
havior can be viewed as a sequence of speci“c components
that vary across the life-cycle. Thus, just as biological and en-
vironmental factors can exert main and interactive effects to
determine susceptibility, so too can they in”uence the likeli-
hood of maintaining tobacco dependence once it is estab-
lished, response to treatment for tobacco dependence, and
the likelihood of relapse following treatment. This chapter re-
views state-of-the-art “ndings and poses questions in need of
further investigation.
Tobacco smoke, inhaled either directly or as second-hand
smoke, contains more than 4,000 different compounds,
many of which are proven carcinogens (Roberts, 1988).
There is substantial evidence suggesting that nicotine plays a
pivotal role in mediating the addictive nature of tobacco in
humans U.S. Department of Health and Human Services
([USDHHS], 1988). Nicotine is readily absorbed across the
respiratory tract epithelium, buccal mucosa (cheek), and
skin. Systemic bioavailability through the gastrointestinal
tract is limited because of “rst-pass liver metabolism. After
inhalation, nicotine reaches the brain in approximately 10 to
19 seconds (Benowitz, Porchet, Sheiner, & Jacob, 1988), re-
sulting in rapid onset of behaviorally reinforcing effects on
the nervous system, including pleasure, relief of anxiety, im-
proved task performance, improved memory, mood modula-
tion, and skeletal muscle relaxation (Benowitz, 1999). These
Preparation of this chapter was supported in part by grants from
the Tobacco-Related Disease Research Program, University of
California (7PT2000), the National Cancer Institute (CA71358),
and the National Institute on Drug Abuse (DA11170). The authors
wish to thank Ms. Kymberli Hemberger for her assistance with the
preparation of this manuscript.