Biology Reference
In-Depth Information
N
EUROCHEMICAL
E
VIDENCES FOR THE
I
NVOLVEMENT OF THE
D
ORSAL
S
TRIATUM IN
D
RUG
A
DDICTION
The involvement of the dorsal striatum in drug addiction may have important
neurobiological implications that could be crucial in determining the clinical evolution of the
disease. In fact, the dorsal striatum works together with the NAc in order to execute actions.
The dorsal striatum receives dopaminergic innervation from the midbrain that can be
functionally modified by chronic drug consumption. Moreover, the intrinsic neuronal cells
within the dorsal striatum receive glutamatergic innervation from the PFC.
The involvement of the dorsal striatum and its dopaminergic innervation in human
addiction has been detected in neuroimaging techniques. A recent study published by Volkow
et al. (2006) examined the influence of stimuli paired with cocaine (conditioned stimuli) on
the response of the dorsal striatum. That is, neuronal responses were registered when subjects
were watching a neutral video (nature scenes) versus when they were watching a cocaine-cue
video (scenes of subjects smoking cocaine). The study tested eighteen cocaine-addicted
subjects that underwent PET scan using [
11
C]raclopride as a radiolignad for dopamine D2
receptor. Patients fulfilled Diagnostic and Statistical Manual of Mental Disorders, Fourth
Edition (DSM-IV) criteria for cocaine dependence and were active cocaine users for at least
the previous 6 months. The feelings of craving experienced by abstinent human addicts were
examined using the Brief Version of the Cocaine Craving Questionnaire (CCQ) (Tiffany et
al., 1993), which evaluates current cocaine craving (desire, intention, and plan to use,
anticipation of positive outcome, anticipation of relief from withdrawal or distressing
symptoms, and lack of control over drug use) on a seven-point visual analog scale. The study
measured dopamine release through changes in dopamine receptor availability (though PET)
by comparing the specific binding of [
11
C]raclopride when subjects were watching a neutral
video (nature scenes) and when they were watching a cocaine-cue video
(scenes of addicts
smoking cocaine). The results showed an increase in dopamine in the dorsal striatum
(caudate, putamen) in cocaine-addicted subjects when they were watching the cocaine-cue
video (see figure 7). The increase in extracellular DA in the striatum was proportional to the
increase in cocaine craving. Subjects with more severe addiction had larger DA increases in
response to conditioned stimuli than subjects with less severe addiction. The main projection
from dopaminergic cells in the midbrain to the dorsal striatum, which is involved in habit
learning, arises from the substantia nigra (Haber and Fudge, 1997). This implicates the DA
nigrostriatal pathway and the dorsal striatum in the subjective experience of craving that often
lead to relapse (Volkow et al., 2006). The association between dorsal striatal dopaminergic
activity and cue-induced cocaine craving could reflect the habit-based (automatized) nature of
craving in addiction.
Consistent with the findings of Volkow (2006), various studies using animal models also
reported the involvement of the dorsal striatum and its dopamine and glutamate afferences in
drug addiction. Early experiences with cocaine mainly involve the limbic striatum
(motivational and affective functions). In contrast, as exposure to cocaine continues, the
impact of cocaine progressively affects the dorsal striatum (cognitive and sensoriomotor
functions) (Porrino et al., 2004). Whereas the acquisition of the drug-seeking behavior
depends on the NAc core (Di Ciano and Everitt, 2004), the control over the performance of
the behavior depends on the dorsal striatum (Vanderschuren et al., 2005). Both dopamine
