Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
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Neuropsychopharmacology · May 2006
The striatal and extrastriatal D2/D3 receptor-binding profile of clozapine in patients with schizophrenia.
Positron emission tomography (PET) studies reveal that clozapine at clinically used doses occupies less than 60% of D2/D3 dopamine receptors in human striatum. Here, the occupancy of D2/D3 dopamine receptors by clozapine in patients with schizophrenia was determined to test the hypothesis that clozapine binds preferentially to extrastriatal dopamine receptors. A total of 15 clozapine-treated inpatients with schizophrenia underwent a [18F]fallypride PET scan. ⋯ Occupancy of cortical receptors approaches 60% with plasma clozapine in the range 350-400 ng/ml, which corresponds to the threshold for antipsychotic efficacy of clozapine. Extrastriatal binding of clozapine may be more relevant to its antipsychotic actions than striatal. However, further studies with an intraindividual comparison of untreated vs treated state are desirable to confirm this finding.
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Neuropsychopharmacology · May 2006
Systemic and intra-amygdala administration of glucocorticoid agonist and antagonist modulate extinction of conditioned fear.
We examined the effect of glucocorticoid agonists on the extinction of conditioned fear in rats by using fear-potentiated startle. Systemic injection of glucocorticoid receptor agonists dexamethasone (DEX) (0.1, 0.5, and 1.0 mg/kg) and intra-amygdala infusion of RU28362 (0.5, 1.0, and 3.0 ng/side) prior to extinction training facilitated extinction of conditioned fear in a dose-dependent manner. Extinction of conditioned fear and circulating corticosterone levels were attenuated by administration of corticosteroid synthesis inhibitor metyrapone (25 mg/kg s.c.) 90 min before extinction training. ⋯ The Dose of dexamethsone or metyrapone used here did not influence fear-potentiated startle when administered before testing. Thus, it is unlikely that these drugs influenced extinction by increasing or disrupting CS processing. All results suggested that amygdaloid glucocorticoid receptors were involved in the extinction of conditioned fear.
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Neuropsychopharmacology · Apr 2006
Dysfunctional attentional networks in children with attention deficit/hyperactivity disorder: evidence from an event-related functional magnetic resonance imaging study.
Although there is evidence for attentional dysfunction in children with attention deficit/hyperactivity disorder (ADHD), the neural basis of these deficits remains poorly understood. ⋯ Our results demonstrated altered brain mechanism in ADHD associated with all three attentional networks investigated. For alerting and executive attention, our data indicate a deviant mechanism of cortical control, while ADHD children may have adopted altered strategies for reorienting of attention. Our results also stress the etiological role of functional abnormalities in the putamen in medication-naive ADHD.
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Neuropsychopharmacology · Apr 2006
Comparative StudyChronic pain induces anxiety with concomitant changes in opioidergic function in the amygdala.
Clinically, it has been reported that chronic pain induces depression, anxiety, and reduced quality of life. The endogenous opioid system has been implicated in nociception, anxiety, and stress. The present study was undertaken to investigate whether chronic pain could induce anxiogenic effects and changes in the opioidergic function in the amygdala in mice. ⋯ In the light-dark test, the time spent in the lit compartment was not changed at 8 weeks after surgery. Collectively, the present data constitute the first evidence that chronic pain has an anxiogenic effect in mice. This phenomenon may be associated with changes in opioidergic function in the amygdala.
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Neuropsychopharmacology · Mar 2006
Comparative StudyEffects of background and prepulse characteristics on prepulse inhibition and facilitation: implications for neuropsychiatric research.
Both prepulse inhibition (PPI) and prepulse facilitation (PPF) deficits have been reported in schizophrenia patients, but the use of different experimental parameters across laboratories makes direct comparisons of results difficult. We assessed the effects of different parameters on PPI and PPF in normal subjects. ⋯ Paradigmatic differences appear likely to be responsible for divergent findings in studies of PPI and PPF in normal and schizophrenia subjects. The present study should guide investigators in the selection of parameters for assessing PPI and PPF in studies of normal subjects and schizophrenia patients. Attention to the 4 factors of 1) background noise, 2) prepulse duration, 3) frequency, and 4) interval will facilitate comparability of results across different laboratories, especially when using PPI/PPF in schizophrenia research as neural substrate probes, as biomarkers, and as endophenotypes.