Substance Use Disorders 397
9.6 • Cocaine Abuse
and Dependence and
Dopamine This schematic
illustrates how cocaine binds to
dopamine transporters, which
prevents normal reuptake of
dopamine back into the transmitting
neuron and increases the amount
of dopamine in the synapse, which
thereby activates the dopamine
reward system.
by altering other brain areas or neurotransmitters that, in turn, affect dopamine
(Leone, Pocock, & Wise, 1991).
Regular stimulant use (or other substance use) usually affects the dopamine
reward system. Researchers have thus proposed the dopaminergic hypothesis of
substance abuse: The rewarding effects of a drug arise directly or indirectly from
the dopamine reward system (Koob & Le Moal, 2008; Robbins & Everitt, 1999a,
1999b; Tomkins & Sellers, 2001; Torrens & Martín-Santos, 2000). Because of the
neural changes that occur with continued abuse, after a while, the person needs
the substance to feel “normal” and experiences cravings when not using the drug.
As researchers have come to understand the dopamine reward system in more
detail, they have begun to gain insight into an age-old puzzle: Why are some people
more susceptible to becoming abusers than others? Do they have less “character”
or a weak “moral compass”? No. In fact, at least part of the answer is that the do
amine reward system is more sensitive and responsive in some people. For example,
in one study, participants were given an injection of the stimulant Ritalin. The re-
searchers found that participants who rated the experience as pleasant had fewer
dopamine receptors than those who found it unpleasant (Volkow et al., 1999). Such
fi ndings support the hypothesis that people with fewer dopamine receptors may be
more vulnerable to drug use (and abuse); the smaller quantity of receptors means
they have reduced activation in the reward system, which is boosted by substance
use (Swanson & Volkow, 2002). In fact, rats bred so that they consume relatively
high amounts of alcohol appear to have a less responsive dopamine reward system,
which could explain why they drink more (McBride et al., 1990).
In addition, as we’ll discuss shortly, stimuli related to taking a drug—such as
the music, lighting, and crowds at a dance club where cocaine use occurs—can be-
come associated with drug use. Connections among different brain areas, such as
the amygdala and hippocampus, store associations between drug use and the stim-
uli related to drug use. Once such associations are established, these drug-related
stimuli themselves can trigger the dopamine reward system (Tomkins & Sellers,
2001). Moreover, simply perceiving such aspects of the environment can activate
structures in the limbic system (Dackis & O’Brien, 2001), which is tightly tied to
the dopamine reward system. For ex-
ample, one such structure is the an-
terior cingulate, and an fMRI study
found that this structure was activated
when cocaine addicts simply watched
videotapes of cocaine-related objects
and events (Wexler et al., 2001).
Effects of Cocaine and
Methamphetamine on the Brain
To see how the dopamine reward sys-
tem is involved in drug abuse, let’s
look at two abused drugs, cocaine and
then methamphetamine. The effects of
cocaine on the brain result from the
way it affects dopamine levels. Spe-
cifically, cocaine binds to dopamine
transporters—the molecules that take
excess dopamine from the synapse and
bring it back to dopamine containing
sacs within the terminal buttons of the
transmitting neuron (see Figure 9.6).
When cocaine binds to these trans-
porter molecules, they don’t operate as
effectively to remove dopamine from
the synapses—and thus more dopamine
Figure 9.6
99
a
D
il
d p d n o t r
g9
Dopamine
receptors
Receiving
neuron
Dopamine
packaged
in sacs
Transmitting
neuron
Cocaine
Dopamine
transporter
blocked by
cocaine
Dopamine
transporter
functioning
normally