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4. PSYCHOPHARMACOLOGY OF DEPENDENCE FOR DIFFERENT DRUG CLASSES

BOX 4.6

Use of stimulant drugs to treat attention deficit hyperactivity
disorder
Attention deficit hyperactivity disorder (ADHD) is characterized by hyperactivity,
impulsivity and deficits in attention that are not appropriate for a child’s
developmental age. Psychostimulants, such as methylphenidate, are used in the
treatment of ADHD. This use may seem paradoxical, however, it is believed that
individuals with ADHD have low norepinephrine and dopamine activity and therefore
have poor attention and difficulty in regulating behaviour based on external stimuli.
The neurotransmitters norepinephrine and dopamine promote sensory and motor
arousal. With too little cortical arousal, it is thought that subcortical emotional
systems govern behaviour impulsively. When cortical arousal is facilitated with
psychostimulants, the attention of children with ADHD improves and they are
more able to concentrate on a task. Thus, with improved attention, individuals
with ADHD can better regulate their own behaviour.
Source: Panksepp, 1998.

Amphetamine is a potent psychotomimetic, and can intensify symptoms
or precipitate a psychotic episode in vulnerable individuals (Ujike, 2002).
People who use amphetamine chronically often develop a psychosis very
similar to schizophrenia (Robinson & Becker, 1986; Yui et al., 1999).
Amphetamine is readily self-administered by animals (Hoebel et al., 1983),
shows robust place preference conditioning (Bardo, Valone & Bevins, 1999),
discriminative stimulus effects (Bevins, Klebaur & Bardo, 1997), and brain
stimulation reward effects (Phillips, Brooke & Fibiger, 1975; Glick, Weaver &
Meibach, 1980).
Mechanism of action
The primary mechanism of action of amphetamine is to stimulate the release
of dopamine from nerve terminals via the dopamine transporter. Thus,
dopamine can be released independently of neuronal excitation. This
contrasts with the effects of cocaine, which blocks the reuptake of
monoamines in the nerve terminal, and thus only affects active neurons. Like
cocaine, amphetamine also inhibits, to a certain extent, the reuptake of the
catecholamines, thereby increasing their ability to activate receptors.
Amphetamine may also directly activate catecholamine receptors, further
contributing to monoaminergic activity.

Tolerance and withdrawal
Tolerance develops rapidly to many of the behavioural and physiological
effects of amphetamines, such as suppression of appetite, insomnia,
euphoria, and cardiovascular effects (Jacobs & Fehr, 1987). Interestingly, the

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