Biology Reference
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cingulate regions, which are involved in high-order cognitive and motivational functions.
Therefore, the ability to modulate the salience of a reinforcer to update reward-related
information, such as learning new rewarded responses, to inhibit the response when it is no
longer adaptive and to control a prepotent response are compromised in drug addicts (Volkow
et al., 1992; Goldstein and Volkow 2002; Goldstein et al., 2007). In addiction, hypofrontality
is a strong indicator of reduced ability to regulate drug-seeking behavior.
Reduced metabolism in the prefrontal cortex of cocaine abstinent patients was found even
after 3 months of abstinence (Volkow et al., 1992). These data show that the effects of
chronic cocaine use on the brain are long-lasting and suggest the possibility that these
metabolic changes are induced by transient neuronal adaptation and even long-lasting
neuroplastic changes. Studies using structural neuroimaging have provided evidence for a
volume reduction involving cortical and subcortical limbic structures in cocaine addicts
(Franklin et al., 2002). It has been suggested that this volume reduction in different brain
regions (from 5% to 11%) reflects a decreased neuronal tissue as a consequence of the
repeated drug consumption. These effects involving abnormalities in neuronal tissue are long-
lasting and even permanent. Nevertheless, it is not known if the hypofrontality and altered
cerebral tissue precedes or is a consequence of the long-term neuroadaptation induced by
chronic psychostimulant use.
Other important aspects of drug addiction indicative of neuroadaptive changes as a
consequence of chronic cocaine consumption are those related to the dopamine receptors.
Human addicts also show reduced expression of D2 receptors in the striatum (Volkow et al.,
1993, 2001) that persists some moths after the last cocaine intake (Volkow et al., 1993). This
reduced density of D2 receptors
can be a consequence of chronic drug consumption but can
also exist previous to any contact with the drug, and hence could indicate a predisposition to
addiction (Corominas-Roso et al., 2007).
Cue-stimuli induce craving and relapse in cocaine addicts
A key characteristic of addiction is that situations or stimuli (i.e., cue stimuli) previously
associated with drug seeking or drug taking behavior (e.g., people, places, paraphernalia) can
precipitate in abstinent abusers or addicts an intense emotional response and desire for drug,
known as cravings. Craving have important clinical consequences as it frequently leads to
drug seeking behavior and relapse. Cue stimuli can precipitate relapse even in individuals
who have decided never to use drugs again, often without the addicted person having insight
into what is happening to them (O'Brien et al., 1990, 1998). Drug conditioned cues can be
environmental or can even be interoceptive body states. Cue-induced cravings are often
accompanied by different signs and symptoms similar to the effects of cocaine itself,
including generalized arousal, palpitations, ear ringing, and euphoria (Childress et al., 1993).
In the study of Childress et al. (1999), brain responses to cue stimuli have been conducted
using PET scans or functional magnetic resonance imaging (fMRI). The protocols of
obtaining such measures were similar to those used to evaluate brain responses during
abstinence. But these protocols included, in addition to the scan obtained at rest conditions,
one or more scans obtained with the patient engaged in watching drug-related images and
non-drug related images. The non-drug images, included pictures of nature and are used as a
