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4. PSYCHOPHARMACOLOGY OF DEPENDENCE FOR DIFFERENT DRUG CLASSES

Cocaine (hydrochloride and crack)

Introduction
Cocaine is a powerful nervous system stimulant that can be taken
intranasally, injected intravenously or smoked. The use of cocaine by many
different cultures dates back for centuries. Cocaine is found in the leaves of
Erythroxylon coca, trees that are indigenous to Bolivia and Peru.

Behavioural effects

Cocaine increases alertness, feelings of well-being and euphoria, energy
and motor activity, feelings of competence and sexuality. Anxiety, paranoia
and restlessness are also frequent. Athletic performance may be enhanced
in sports where sustained attention and endurance is required. With
excessive dosage, tremors, convulsions and increased body temperature are
detected. Activation of the sympathetic nervous system occurs
concomitantly with the behavioural effects. Tachycardia, hypertension,
myocardial infarct and cerebrovascular haemorrhages may occur during
cocaine overdose. As the effects of the drugs subside, the user feels
dysphoric, tired, irritable and mildly depressed, which may lead to
subsequent drug use to regain the previous experience (O´Brien, 2001).
There have been numerous papers reporting that cocaine can be self-
administered by animals via the intravenous and oral routes (Caine & Koob
1994; Barros & Miczek, 1996; Rocha et al., 1998; Platt, Rowlett & Spealman,
2001). Cocaine’s augmentative effect on intracranial self-stimulation requires
activation of both D and D dopamine receptors (Kita et al., 1999).
1 2
Conditioned place preference can be induced in rodents by administration
of cocaine (Itzhak & Martin, 2002).

Mechanism of action

In the brain, cocaine acts as a monoamine transporter blocker, with similar
affinities for dopamine, serotonin, and norepinephrine transporters (Ritz,
Cone & Kuhar, 1990). Cocaine, and the dopamine transporter to which it
binds, can be visualized in the human brain using positron emission
tomography (PET) imaging (Fig. 4.2). The antagonism of the transporter
proteins leaves more monoaminergic neurotransmitters available in the
synaptic cleft to act upon presynaptic and postsynaptic receptors. It is widely
accepted that the ability of cocaine to act as a reinforcer is due largely to its
ability to block dopamine reuptake (Wise & Bozarth 1987; Woolverton &
Johnson 1992; Sora et al., 2001). The reinforcing effects of psychostimulants
are associated with increases in brain dopamine and D receptor occupancy
2
in humans as noted in PET studies (Volkow et al., 1999). However, both D
1
and D receptors have been implicated in the reinforcing effects of cocaine.
2
It has been demonstrated in animal studies that D and D -like receptor
1 2
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