Chapter 8 
drug was administered, which responses are being measured, and other 
factors (Henningfield and Keenan, 1993; Pomerleau and Rosecrans, 1989). 
If people with histories of drug abuse are given nicotine, they like the 
nicotine; that is, liking scale scores increase with greater doses within a 
certain range of parameters (Henningfield et al., 1985). Among drug abusers, 
similar findings are reported for morphine and amphetamines but not for 
drugs that have little psychoactivity (Fischman and Mello, 1989). Such 
psychoactive effects are predictive of addiction potential and are correlated 
with the ability of a drug to serve as a reinforcer for animals and humans 
(Griffiths et al., 1980). Nicotine is psychoactive in humans and is readily 
discriminated by animals; several forms of nicotine delivery have been shown 
to serve as reinforcers for animals and humans (U.S. Department of Health 
and Human Services, 1988). 
Physical The cellular and neurological changes that lead to tolerance 
Dependence also lead to physical dependence so that when people abruptly 
and Withdrawal discontinue tobacco use, withdrawal occurs (U.S. Department of 
Health and Human Services, 1988). Withdrawal onset begins within a few 
hours of the last cigarette; symptoms include decreased cognitive capabilities 
and heart rate and increased dysphoria or depressed mood, insomnia, 
craving, anxiety, irritability, restlessness, appetite, and tendency to smoke 
(American Psychiatric Association, 1994; Hughes and Hatsukami, 1992). 
Altered brain electrical potentials and hormonal output are generally opposite 
in direction of those produced by acute nicotine administration, and 
decrements in evoked electrical potentials of the brain indicate impaired 
information processing capabilities (Pickworth et al., 1989; U.S. Department 
of Health and Human Services, 1988). 
Nicotine dependence seems to be mediated primarily by the activation 
of nicotinic cholinergic receptors in the brain (U.S. Department of Health 
and Human Services, 1988) and secondarily through the cascading effects 
of nicotinic systems to modulate levels of hormones such as epinephrine 
(adrenaline) and cortisol (Pomerleau and Pomerleau, 1984; U.S. Department 
of Health and Human Services, 1988). The mesolimbic dopaminergic 
reward system, which mediates the ability of cocaine to produce dependence, 
also has been implicated in nicotine dependence (Corrigall, 1991; U.S. 
Department of Health and Human Services, 1988). The cells of this system 
are located in the ventral tegmental area of the midbrain. Axons project to 
the limbic system — specifically, to the nucleus accumbens, olfactory tubercle, 
nuclei of the stria terminalis, and parts of the amygdala. Behaviors followed 
by such neural activation can become extremely persistent. Cortical effects 
of nicotine administration include changes in local cerebral metabolism 
(London and Morgan, 1993) and electroencephalogram results Qones, 1987). 
Prominent endocrine effects include release of catecholamines, serotonin, 
prolactin, growth hormone, arginine vasopressin, beta-endorphin, and 
adrenocorticotropic hormone (Pomerleau and Pomerleau, 1984; U.S. 
Department of Health and Human Services, 1988). These effects mediate 
both the positive nicotine reinforcement sought by smokers and even 
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