Neurotoxicity research
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Neurotoxicity research · Dec 2006
ReviewDopaminergic dysbalance in distinct basal ganglia neurocircuits: implications for the pathophysiology of Parkinson's disease, schizophrenia and attention deficit hyperactivity disorder.
The basal ganglia form a forebrain system that collects signals from a large part of the neocortex, redistributes these cortical inputs both with respect to one another and with respect to inputs from the limbic system, and then focuses the inputs of this redistributed, integrated signals into particular regions of the frontal lobes and brainstem involved in aspects of motor planning and motor memory. Movement disorders associated with basal ganglia dysfunction comprise a spectrum of abnormalities that range from the hypokinetic disorder (from which Parkinson's disease, PD, is the best-known-example) at one extreme to the hyperkinetic disorder (exemplified by Huntington's disease and hemiballism) at the other. In addition to disorders of movement, major mental disorders including schizophrenic-like states and attention deficit hyperactivity disorder (ADHD) have been linked to abnormalities in the basal ganglia and their allied nuclei. ⋯ DAT knockout mice display a phenotype with increased locomotor activity, which is normalized by psychostimulant treatment. Finally, imaging studies demonstrated an increased density of DAT in the striatum of ADHD patients. Which system is disturbed and whether this system is hyper- or hypoactive is not unambiguously known yet.
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Neurotoxicity research · Oct 2006
ReviewDisruption of cortical-limbic interaction as a substrate for comorbidity.
The prefrontal cortex exerts a potent regulatory influence over subcortical systems that are involved in the regulation of affective states. In particular, the amygdala is a region that is known to play a prominent role in the expression of emotions, and this function is believed to be disrupted in affective disorders and drug abuse. In addition, dysfunction of the prefrontal cortex is believed to be a common element in many psychiatric disorders such as schizophrenia. ⋯ In particular, the ability of the prefrontal cortex to modulate amygdala activity is likely to play an important role in our ability to cope with stressors. We propose that a dysfunction within the prefrontal cortex disrupts the ability of this region to effectively modulate the amygdala, leaving the organism susceptible to detrimental effects of stressors. This would appear to be a common underlying process that may leave the individual susceptible to drug abuse and to the onset or exacerbation of psychiatric disorders such as schizophrenia and depression.