|Addiction Science Network
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As described in the Primer
on Drug Addiciton, the pharmacological activation of brain reward
systems is largely responsible for producing a drug's potent addictive
properties. Personality, social, and genetic factors may also be important,
but the drug's effects on the central nervous system (CNS) remain the primary
determinants of drug addiction. Nonpharmacological factors are likely to
be important in influencing initial drug use and in determining how rapidly
an addiction develops. For some substances, nonpharmacological factors
may interact with the drug's pharmacological action to produce compulsive
substance use. In these cases, "addictive behavior" may involve use of
substances that are generally not considered addictive.
Mesolimbic Dopamine Neurons
Dopamine is one of a number of neurotransmitters found in
the central nervous system. Dopamine has received special attention from
psychopharmacologists because of its apparent role in the regulation of
mood and affect and because of its role in motivation and reward processes.
Although there are several dopamine systems in the brain, the mesolimbic
dopamine system appears to be the most important for motivational processes.
Some addictive drugs produce their potent effects on behavior by enhancing
mesolimbic dopamine activity.
Normal Dopamine Activity
Cells in the mesolimbic dopamine system are spontaneously
active -- action potentials are constantly generated at a slow rate. This
releases small amounts of dopamine into the synaptic cleft. The levels
of dopamine produced when the cells are active at this low rate may be
responsible for maintaining normal affective tone and mood. Some scientists
speculate that some forms of clinical depression may result from unusually
low dopamine levels.
Heroin-Enhanced Dopamine Activity
Heroin increases the neuronal firing rate of dopamine cells.
The increased number of action potentials produce an increase in dopamine
release. The increased dopamine activity increases the effects mediated
by postsynaptic dopamine. The heroin user experiences the enhanced dopamine
activity as mood elevation and euphoria. When the pharmacological action
terminates (i.e., the heroin is eliminated from the brain), the drug user
is highly motivated to repeat this experience.
Cocaine-Enhanced Dopamine Activity
Cocaine inhibits the reuptake of dopamine. This increases
the availability of dopamine in the synapse and increases dopamine's action
on the postsynaptic neurons. The enhanced dopamine activity produces mood
elevation and euphoria. Cocaine's effect is usually quite short, prompting
the user to repeatedly administer cocaine to re-experience its intense
Combined Heroin- and Cocaine-Enhanced Dopamine Activity
Because heroin and cocaine work on different parts of the
mesolimbic dopamine neurons, they can be combined to produce even more
intense dopamine activation. (The heroin increases cell firing and dopamine
release, while the cocaine keeps the released dopamine in the synaptic
cleft longer thereby intensifying and prolonging its effects.) The combination
of heroin and cocaine is known by users as a "speed-ball." This combination
of drugs is extremely dangerous, and users show very rapid psychological
and physiological deterioration.
Although speed-ball use produces extremely intense activation
of brain reward systems, it is often short-lived because this drug combination
is associated with a very high fatality rate. The combination of cocaine
and heroin is perhaps the most dangerous form of illicit substance use;
cocaine and heroin addicts usually avoid this combination of drugs.
model of brain reward circuitry. The brain has specialized pathways
that mediate reward and motivation. Direct electrical stimulation of the
medial forebrain bundle (MFB) produces intensely rewarding effects. Psychomotor
stimulants and opiates can also activate this reward system by their pharmacological
actions in the nucleus accumbens and ventral tegmental area, respectively.
The ventral tegmental action of opiates probably involves an endogenous
opioid peptide system (ENK), but the anatomical location of that system
has not yet been identified. Natural rewards (e.g., food, sex) and other
substances (e.g., caffeine, ethanol, nicotine) may also activate this brain
reward system. (From Bozarth, 1987: Ventral Tegmental Reward System. ©
1987 Raven Press)
In addition to their acute effects described above, repeated
use of psychomotor stimulants like cocaine and opiates like heroin produces
changes in the mesolimbic dopamine system. Specifically, repeated use of
cocaine or heroin can deplete dopamine from this system. These dopamine
depletions may cause normal rewards to lose their motivational significance
(i.e., produce motivational toxicity). At the same time, the mesolimbic
dopamine system becomes even more sensitive to pharmacological activation
by psychomotor stimulants and by opiates (i.e., sensitization develops).
These neuroadpative changes are probably critical for producing an addiction.
Substances that activate the mesolimbic dopamine system without producing
these neuroadaptive effects are probably not truly addictive.
For more information on the role of dopamine in motivation
and reward, see
Pleasure Systems in the