Brain structure & function
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Cortico-ventral basal ganglia circuitry is associated with a variety of mental health disorders including obsessive-compulsive disorder and drug addiction, disorders that emerge during childhood through young adulthood, a period in which the cortex and striatum continue to development. Moreover, cell proliferation, which is associated with development and plasticity, also continues in the cortex and striatum through adulthood. Given the implication of cortico-basal ganglia circuitry in diseases emerging during postnatal development, we studied cell proliferation at different ages in striatal regions associated with specific frontal cortical areas. ⋯ Finally, throughout the juvenile years, the ventral striatal areas receiving input from the ventral, medial prefrontal cortex and orbital prefrontal cortex have significantly more new cells compared to other striatal regions. Integrity of the ventral striatum is critical for the development of goal-directed behaviors. The high number of new cells in the ventral striatum during postnatal development may be particularly important for the refinement of the cortico-striatal network, and in the formation of neural ensembles fundamental to learning during behavioral development.
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Studies reviewed here implicate the extended amygdala in the negative affective states and increased drug-seeking that occur during protracted abstinence from chronic drug exposure. Norepinephrine (NE) and corticotropin-releasing factor (CRF) signaling in the extended amygdala, including the bed nucleus of the stria terminalis, shell of the nucleus accumbens, and central nucleus of the amygdala, are generally involved in behavioral responses to environmental and internal stressors. Hyperactivity of stress response systems during addiction drives many negative components of drug abstinence. ⋯ Many of these stress-associated behaviors are reversed by NE or CRF antagonists given systemically or locally within the extended amygdala. Finally, increased Fos activation in the extended amygdala and NTS is associated with the enhanced preference for drugs and decreased preference for natural rewards observed during protracted abstinence from opiates and cocaine, indicating that these areas are involved in the altered reward processing associated with addiction. Together, these findings suggest that involvement of the extended amygdala and its noradrenergic afferents in anxiety, stress-induced relapse, and altered reward processing reflects a common function for these circuits in stress modulation of drug-seeking.
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The circuit-related consequences of activating the ventral pallidum (VP) are not well known, and lacking in particular is how these effects are altered in various neuropathological states. To help to address these paucities, this study investigated the brain regions affected by VP activation by quantifying neurons that stain for Fos-like immunoreactivity (ir). Fos-ir was assessed after intra-pallidal injections of the excitatory amino acid agonist, NMDA, or the GABA(A) antagonist, bicuculline in normal rats and in those rendered Parkinsonian-like by lesioning dopaminergic neurons with the neurotoxin, 6-OHDA. ⋯ Comparisons of responses to intra-VP NMDA between the hemispheres ipsilateral and contralateral to the lesion revealed that Fos-ir cells in the pedunculopontine nucleus was reduced by 62%, whereas Fos-ir for the basolateral amygdala and STN was reduced by 32 and 42%, respectively. These findings support the concept that the VP can influence both the basal ganglia and the limbic system, and that that the nature of this influence is modified in an animal model of PD. As the VP regulates motivation and cognition, adaptations in this system may contribute to the mood and mnemonic disorders that can accompany PD.