Biology Reference
In-Depth Information
The dorsal striatum includes the caudate and putamen nuclei, which from the functional
point of view involve the associative (caudate and central putamen) and motor striatum
(dorsolateral caudate and putamen, whereas the ventral regions of the striatum constitute the
limbic striatum (Haber et al., 2000).
Striatal neurons receive afferents that have their origin in the mesencephalic substantia
nigra and ventral tegmental area, as well as excitatory inputs that arise from cortical and
subcortical regions, and integrate glutamatergic and dopaminergic signals within the striatal
cells (Kotter, 1994; Starr, 1995). The major neuronal cells in the striatum are the GABAergic
medium spiny neurons which receive inputs from the PFC, amygdala and hippocampus,
synapsing on the head of spiny neurons, whereas subcortical dopamine synapse on the neck
or nearby dendritic shaft (Groves et al., 1994). In turn, striatal cells send projections to the
VTA and substantia nigra (SN) while the midbrain dopamine cells project to the striatum.
This system creates a loose topographical organization in which the VTA and the medial SN
are associated with the limbic striatum whereas the lateral and ventral SN are associated with
the associative and motor striatum. This structural organization provides a directional flow of
information between regions that allow the ventral striatum to influence motor output, via
striato-nigral-striatal pathways (Haber et al., 2000).
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Whereas the VTA is involved in the early transient stages of cocaine sensitization, the
striatum is crucial in the consolidation of drug-induced sensitization. Sensitization is an
increase in locomotor activity induced by repeated cocaine intake and is essentially caused by
the intrinsic properties of addictive drugs. Nevertheless, in drug addiction other processes
regarding reward-related learning are also involved. This kind of learning is even more
crucial than sensitization in the process that advances from initial sporadic impulsive drug
intake to the compulsive consumption that characterizes addiction.
In the context of drug addiction, environmental stimuli that are closely associated in time
and space with the effects of drugs of abuse can acquire secondary reinforcing properties
through a process of classical conditioning. Once conditioned, these stimuli have in
themselves the ability to elicit the emotional responses that were induced by the drug during
active consumption. These cue-conditioned stimuli are able to maintain drug seeking behavior
and relapse, even after long-term abstinence (O'Brien et al., 1992). Neuroimaging studies
have revealed the neural structures activated when abstinent addicts are watching images
related to drug consumption. Activation in those brain regions are involved in the feeling of
craving that often leads to relapse (Childress et al., 1999; Garavan et al., 2000).
The role of conditioned stimuli in drug addiction has been widely studied through animal
models of abstinence and relapse. For example, in a study by Grimm et al. (2003), rodents
were trained to self-administer cocaine or sucrose as a comparative vehicle. Training was
conducted with a continuous reinforcement schedule (each lever press is reinforced with
cocaine) administered in six daily sessions for 10 days. Each earned reward was accompanied
by a five-second tone-light cue. Afterwards, there was a withdrawal phase during which rats
were housed in the animal facility. Then, rats were separated in three groups and were tested
