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striatum dopamine action is required because administration D1 and D2 receptor antagonist
prevented depotentiation in corticostriatal synapses (Centonze et al., 2006).
LTP is enhanced using the D2 receptor antagonist L-sulpiride whereas the D2-selective
receptor agonist quinpirole not only blocks LTP but also reveals LTD (Calabresi et al.,
1997b). Blockade of D1 or D5 receptors using specific antagonists stop corticostriatal LTP
(Centonze et al., 2003). This suggest that stimulation of D1-like receptors is necessary for the
induction of LTP in the dorsal striatum. Both D1 and D2 dopamine receptor stimulation is
required for the induction of the striatal LTD (Calabresi et al., 1992, 1996), while both kind of
receptors appear to act in opposition to one another during the induction of LTP (Centonzee
et al., 1999). It has been proposed that the induction of LTD could require a weaker DA
release in the striatum because DA has a higher affinity for the D2 receptors than the D1
receptors (for a review see Calabresi et al., 2007). Those changes in excitability and synaptic
plasticity in the striatum may lead to the behavior and emotional consequences which
characterize addiction. In the striatum, there is a differential distribution of the two families of
DA receptors, D1-like and D2-like, which makes characterization of the role of dopamine in
the long-lasting striatal synaptic plasticity difficult. In the striatum, D1 and D2 receptors seem
to be segregated in to subpopulations of projecting GABA spiny neurons, which form two
large efferent streams, the direct and indirect pathways. D1 receptors are found predominantly
in the striatonigral neurons of the direct pathway, whereas D2 receptors are mainly expressed
by the striatopallidal neurons of the indirect pathway (Gerfen et al., 1990).
A decrease of the D2 expression in the striatum of cocaine addiction, as well as in other
addictive disorders such as alcohol dependence, has been repeatedly described (Volkow et al.,
1993; Volkow et al., 1996). It has been proposed that a deficit of D2 could exist prior to drug
abuse, a possible vulnerability trait in addicts predisposing them to substance consumption
(Morgan et al., 2002). This condition is sometimes described as a reward deficit syndrome
(Comings and Blum, 2000; Khantzian, 1985). In a design with mice lacking dopamaine D2
receptors, D2 has been observed playing a key role in mechanisms underlying the direction of
long-term changes in synaptic efficacy and plasticity in the striatum. In fact, in rats lacking
D2 in the striatum, high-frequency stimulation of corticostriatal fibers induces NMDA-
dependent LTP instead of LTD. It has been suggested that reduced D2 expression might lead
to loss of high-frequency activation of glutamatergic inputs. This could cause a profound shift
in the direction of long-term excitability at corticostriatal synapses (Calabresi et al., 1997b)
that could lead to changes in the direction of the neuroplastic organization of
corticostriatocortical circuits.
Dendritic spines of striatal neurons have been proposed as being the target anatomical
locus of the interaction between glutamate and dopamine, and also the site of expression of
striatal synaptic plasticity (Calabresi et al., 1997c). Dopamine appears to be necessary for the
maintenance of the health and functional integrity of corticostriatal synapses and it has been
suggested that in the absence of dopamine some of these corticostriatal synapses disconnect
and may even disappear. The loss of spines in the striatum cells takes place over the first three
weeks after lesions with 6-hydroxydopamine, and these cells remain less spiny even after one
year after the lesion (Ingham et al., 1993; Arbuthnott et al., 2000).
