Tobacco and Public Health - TCSC Indonesia

(Fischman and Foltin 1991). Another method for assessing the interoceptive effects of
nicotine is the drug discrimination procedure, in which the perceived stimulus effects
can be directly observed (Preston and Bigelow 1991).
Nicotine, like other dependence-producing drugs, displays drug discrimination,
inducing changes in the central nervous system that are distinct and identifiable.
These changes can be blocked by a central (mecamylamine), but not a peripheral
(trimethaphan) nicotine antagonist, demonstrating that the discriminative stimulus
effects of nicotine are centrally mediated (Perkins et al. 1999b). The discriminative
stimulus effects of nicotine are thought to be critical in understanding both nicotine
reinforcement and addiction as these effects of nicotine may cue further drug-seeking
behavior, supplementing the primary reinforcing effects of nicotine (Jasinski and
Henningfield 1989; Stolerman and Jarvis 1995).
A drug’s discriminative stimulus effect is thought to be closely related to its subjective
effects (Preston and Bigelow 1991). However, unlike subjective effects, the discrimination
procedure uses observable behavioral responses to determine whether a drug’s
stimulus effects have been perceived by the subject (Preston and Bigelow 1991).
Discriminative stimulus effects of nicotine are demonstrated by training subjects
to explicitly associate the drug effect to a specific response that leads to reinforcement
(Di Chiara 2000). In a drug discrimination procedure, subjects learn, through repeated
exposure to the drug, to recognize its interoceptive characteristics and employ these
characteristics to discriminate different drugs or different doses of the same drug
(Duka et al. 2002).
Most human drug discrimination studies use a similar testing method (Perkins et al.
1997). Initially, subjects learn to discriminate nicotine from placebo (Discrimination
Training). During discrimination training, subjects are presented with training doses
of nicotine and placebo that are labeled ‘A’ and ‘B’. During the first presentation of
each, subjects are told which one they received. There are then subsequent presentations,
in random order, in which subjects must guess if they received ‘A’ or ‘B’
(Discrimination Testing). The criterion for reliable discrimination is at least 80%
correct identification of the letter code with ten or fewer sessions. After reliably
discriminating the training dose of nicotine from placebo, subjects are administered a
range of doses for generalization testing to determine how similar these doses are to
the training doses (‘A’ and ‘B’). Using this method, studies have consistently found that
smokers can reliably discriminate nicotine from placebo.
Animal models of nicotine reinforcement
BRIDGETTE E. GARRETT ET AL. 153
Nicotine locomotor stimulant effects
Consistent with its effects in humans, nicotine produces psychostimulant effects in
laboratory animals. Acute nicotine administration produces a dose-dependent, transient
decrease in locomotor activity, followed by a dose-dependent, more prolonged