Tobacco and Public Health - TCSC Indonesia

following repeated, infrequent and even acute nicotine administration are consistent
with its high addiction liability in smokers and suggest that even a seemingly trivial
and/or limited exposure to nicotine can lead to relapse long after cessation of regular
tobacco use.
Nicotine drug discrimination
BRIDGETTE E. GARRETT ET AL. 155
The interoceptive properties of nicotine are thought to be important for their rewarding
effects, dependence and abuse liability. As such, the ability of nicotine to serve as a
discriminative stimulus is likely necessary for nicotine self-administration. To assess
the interoceptive properties of nicotine, rats and more recently mice, are trained typically
to press a lever under a fixed ratio schedule for food reinforcement, although
other more complex operant schedules, such as tandem fixed ratio variable interval
schedules have also been utilized. Once responding stabilizes, nicotine discrimination
training is instituted using a two-lever procedure. On alternating days, nicotine is
administered at a particular training dose; during these experimental sessions, pressing
of one of the two levers results in food pellet reinforcement, whereas pressing the
second lever has no programmed consequence. On alternate days, saline is administered
prior to the session and the lever that delivers food is reversed from the previous
day. Thus, the animal learns to use the presence or absence of the nicotine cue to signal
which lever leads to food reinforcement. Sessions are typically terminated after a
predetermined number of reinforcements are earned or after a predetermined time has
elapsed. Drug discrimination is established when animals reliably make drug- and
saline-appropriate responses under a brief test condition when food reinforcement is
omitted. During subsequent test sessions, dose response for nicotine generalization
may be determined to ascertain if nicotine is discriminated accurately from the vehicle.
Other drugs may be substituted for nicotine to ascertain their ability to generalize to
the discriminative stimulus effects of nicotine (stimulus generalization or substitution
tests). Alternatively, drugs may be administered prior to or concurrently with nicotine to
determine their ability to block the discriminative stimulus of nicotine (stimulus
antagonism tests). In experiments employing humans as the subjects, examples of
subjective effects assessed concurrently with behavioral discrimination reveal that
nicotine discrimination is guided by interoceptive cues such as ‘stimulated’, ‘alert’, and
‘jittery’ (Perkins et al. 1994; Perkins and Stitzer 1998).
Mecamylamine and dihydro-β-erythroidine have been shown to inhibit completely
the discriminative stimulus effects of nicotine in drug discrimination studies
(Stolerman et al. 1984, 1997; Brioni et al. 1994; Shoaib et al. 2000); and thus, the discriminative
stimulus effects of nicotine are mediated by neuronal nicotinic receptors.
Interestingly, the discriminative stimulus effects of nicotine were not attenuated by
methyllycaconitine (Brioni et al. 1996; Gommans et al. 2000), indicating that homomeric
α7 nicotinic receptors are not likely involved. However, more than one subtype