In support of a deficit in the nucleus accumbens shell, giving rise to ADHD behavior in SHRs, Papa et al. (26,27) found decreased calcium/calmodulin-dependent protein kinase II and reduced c-Fos expression only in the nucleus accumbens shell of SHRs and not the core subdivision when compared to WKYs. The mesolimbic dopamine projection to the shell subdivision of the nucleus accumbens is responsible for motivation; it determines the amount of effort an animal is prepared to exert in order to achieve a reward. Hypofunction of the mesolimbic dopamine system will impair the function of the mesocortical and nigrostriatal dopamine systems, by influencing dopamine release and the cortico-striato-thalamo-cortical circuits that dopamine modulates. This could impair learning and expression of goal-directed behavior, thereby contributing to the ADHD symptoms displayed by SHRs.
A deficiency in the mesolimbic dopamine projection to the nucleus accumbens shell will impair dopamine release in the shell and thereby impair dopamine release in the nucleus accumbens core and dorsal striatum, as these areas are controlled by an ascending spiral that connects the striatum to the midbrain dopamine neurons (62). The ascending spiral circuit regulates dopamine release and integrates information across functionally different parallel cortico-striato-thalamo-cortical circuits (62). The nucleus accumbens is the interface between the limbic system and the motor system (62,63). Limbic structures, such as the orbital and medial prefrontal cortex, hippocampus, amygdala, entorhinal, perirhinal, and anterior cingulate cortex, proj ect to the nucleus accumbens and rostral medial caudate nucleus (62,64,65). The nucleus accumbens projects via the ventral pallidum and substantia nigra to the dorsomedial thalamus, which projects to the dorsolateral prefrontal cortex in an ascending spiral (62,64). The dorsolateral prefrontal cortex, together with the posterior parietal cortex, projects to the head of the caudate nucleus and rostral putamen, which, in turn, project via the globus pallidus/substantia nigra to the ventral anterior nucleus of the thalamus and from there to the supplementary motor, premotor, and motor cortex (62,64). The latter, together with the somatosensory cortex, project to the rostral dorsolateral striatum and putamen, which project via the globus pallidus/substantia nigra to the ventrolateral nucleus of the thalamus and back to the supplementary motor cortex, completing the ascending spiral through which the nucleus accumbens shell influences behavioral expression (62,64).
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