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The Biological Basis of Addiction
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 subjective effects.
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; even
cocaine and heroin addicts usually avoid this combination of drugs.
Proposed
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)
Neuroadpative Effects
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.
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