Abnormal Psychology

398 CHAPTER 9

lingers there, which causes the receiving neuron to fi re even when relatively

little dopamine has been released by the sending neuron (Koob & Bloom,

1988; Koob, Sanna, & Bloom, 1998). Thus, relatively little stimulation can

produce pleasurable sensations.

A similar mechanism is at work when someone takes methamphet-

amine. Again, the drug binds to the molecules that transport excess do-

pamine back to the terminal buttons and prevents them from operating

effectively—thereby leaving more dopamine in the synapse, which in turn

activates the dopamine reward system. Long-term use of methamphet-

amine disrupts the functioning of these transporter molecules. Moreover,

as shown in Figure 9.7, not all of the damage infl icted on the brain by long-

term methamphetamine abuse is reversible. The images in the fi gure show

the distribution of dopamine transporters in the brain of a person who

abused methamphetamine. As is evident, even 2 years after the person stopped using

methamphetamine, the neurological effects of chronic abuse are not totally reversed.

Brain Systems and Neural Communication II: Beyond Dopamine

In this book we have emphasized that brain areas work together in systems, and

often more than one system is involved in producing a particular behavior. This is

true of stimulant abuse in particular, and substance abuse in general. Although the

dopamine reward system plays a crucial role in leading people to abuse drugs, it is

not the whole story. Many other neurotransmitters and their related brain systems

have been implicated in drug abuse, but three are particularly important: gamma-

aminobutyric acid (GABA), glutamate, and serotonin.

The GABAnergic system—the term used for the system of neurons that rely on

the neurotransmitter GABA—appears to play a particular role in the shift from rec-

reational use to abuse and dependence (Brady, 2005; Kalivas & Volkow, 2005). The

GABAnergic system includes part of the frontal lobe—in particular, the prefrontal

cortex—that is involved in motivated behavior (that is, behavior oriented toward a

goal) and thus in drug-seeking behavior (Kalivas & Volkow, 2005).

The glutamate system—which consists of neurons that rely on the neurotrans-

mitter glutamate—also plays a role in the shift from drug use to abuse and depen-

dence. Glutamate receptors abound throughout the cortical and limbic regions that

play a role in drug abuse, and researchers have shown that such receptors help

to produce the reinforcing effects of drugs—which lead some people to become

abusers—and also the negative effects experienced during withdrawal (Kenny &

Markou, 2004). In fact, drugs that block glutamate receptors have been used to

treat cocaine dependence and nicotine dependence (Ait-Daoud et al., 2006).

Finally, the serotonin system—which consists of neurons that rely on the neu-

rotransmitter serotonin—plays a role in the abuse of stimulants. This is not surpris-

ing, given that this system is critical for the regulation of many basic biological

functions, such as eating, drinking water, sexual behavior, and response to pain

(Pihl & Peterson, 1995). Serotonin has been shown, for example, to play a role in

producing the desire for cocaine (Aronson et al., 1995).

However, it’s important to remember that the different neurotransmitters and

brain systems work together and that their effects emerge from their interactions. As

we have described, stimulants lead to increased dopamine production in the nucleus

accumbens (and other dopamine-producing areas), and the higher level of dopamine

not only has direct effects on the reward value of drugs but also indirectly modulates

the activity of the GABAnergic, glutamate, and serotonin systems. These systems

can cause the drug to have rewarding effects and make other rewards (such as a

good meal, an interesting conversation, or a paycheck) feel less valuable (Kalivas &

Volkow, 2005).

Thus, although stimulants in general engage the dopamine reward system, this

effect is not the only reason why some people come to abuse such drugs. Some

stimulants also have more specifi c effects on the brain. For example, MDMA not

only causes dopamine to be released, but also binds to serotonin transporters and

9.7 • Methamphetamine Abuse:

Reversible and Irreversible

Brain Damage (a) This scan shows

the distribution of dopamine transporters

in a normal brain. (b) This scan shows

the brain of a person who had used

methamphetamine over a period of

years; as is evident, even 1 month after

this person stopped using the drug, the

dopamine transporters are still in short

supply. (c) This scan shows the brain of

the same abuser more than a year after

stopping the use of methamphetamine;

although there is some recovery of

function, the effects of chronic abuse are

not completely reversed.

Source: Nora D. Volkow et al., The Journal of

Neuroscience, December 1, 2001, 21 (23):9414–9418.

Figure 9.7

bd

(a)No history of (b) (c)

methamphet-

amine use

1 month after

abuse stops

1 year after

abuse stops