Learning and Memory Mechanisms Involved in Compulsive Drug Use and Relapse - Drugs of Abuse: Neurological Reviews and Protocols - page 74

not so diffi cult to get individuals to stop using a drug; the problem is to keep
them from restarting” (6) . Relapse can occur despite months or even years of
abstinence (long after the end of any withdrawal symptoms), and is very often
provoked by specifi c cues or contexts—meeting an acquaintance with whom
the addict previously used drugs, or perhaps passing a location where drugs
were obtained. Any explanation of addiction will therefore need to account
for the specifi city, persistence, and compulsive nature of drug-taking and
relapse.
Humans have particular brain mechanisms for allowing specifi c acquired
behaviors to be persistently expressed, and we call this associative learning.
Associative mechanisms are therefore excellent candidates for both the
specifi city and the persistence of relapse liability. However, most learning
models of addiction have had diffi culty providing a compelling model of
compulsion—the apparent loss of control over drug-taking. (The meaning of
“loss of control” is obviously critical, and is discussed further in Subheading
7. ) Individuals frequently face situations of confl icting goals and desires, and
need to make decisions about which course of action to pursue. If addicts are
able to state clearly to others and to themselves a resolute intention not to
restart drug use, why should they not make the appropriate choice when
faced with drug-related cues? Although people may use drugs for a host of
reasons, including social pressures, novelty-seeking, pleasure-seeking, relief
of withdrawal symptoms, and other forms of self-medication, drug addiction
is essentially a failure of adaptive decision-making.
Some theories have suggested that associative learning has a necessary
but not suffi cient role, and that the dysregulation of some additional process
underlies compulsion. For example, Robinson and Berridge argued that drugs
could produce sensitization of mechanisms underlying “incentive motivation”;
cues associated with drug use would then evoke excessive “wanting” of drugs
(7) . Another, complementary proposal is that dysregulation of homeostatic
mechanisms result in altered reward “set points” (8) and that these act in
conjunction with sensitization processes to produce failed self-regulation of
drug-taking.
The major diffi culty with such ideas is in accounting for specifi city and
persistence in drug addiction. For example, if addicts have generally sensitized
incentive motivation, why don't they show uncontrollable wanting of food or
sex, in addition to drugs? Although there is some evidence that such broad
cross-sensitization might occur in some animal models (9 , 10) , it does not
appear to be a prominent feature of human addiction. Robinson and Berridge
suggested that “The expression of this sensitized system is focused expressly
on stimuli that have become associated with its excessive activation, so drugs
and drug-associated stimuli become irresistibly attractive ('wanted')” (7) . Yet