The density of striatal dopamine D2 receptors has been shown to vary considerably among healthy subjects. 1This variability might be due to genetic or environmental factors. In the present analysis we searched for relationships between dopamine D2 receptor gene (DRD2) polymorphisms and striatal dopamine D2 receptor density in vivo, as measured by positron emission tomography and [ 11 C]raclopride in 56 healthy subjects. There was a significant association between presence of a putative functional DRD2 promoter allele (−141C Del) and high striatal dopamine receptor density (t = 2.32, P = 0.02). In agreement with some previous studies 2-4 the presence of the DRD2 TaqIA1 allele was associated with measures of low dopamine receptor density (t = 2.58, P = 0.01). Also the DRD2 TaqIB1 allele was associated with low dopamine receptor density (t = 2.58, P = 0.01) wheras there was no significant relationship between another common silent intronic DRD2 short tandem repeat polymorphism (STRP) and striatal dopamine D2 receptor density. The results suggest that DRD2 genotypes may participate differentially in the regulation of striatal dopamine D2 receptor density in healthy human subjects. The results should be interpreted with caution because of the limited sample size.Positron emission tomography (PET) has been used to demonstrate a considerable variability of dopamine D2 receptor density in healthy subjects in vivo.1 This variability has recently been associated with the personality trait Detachment, 5 indicating that dopamine D2 receptor density may have functional importance for personality characteristics in human subjects. A fundamental issue is the extent to which the dopamine D2 receptor variability is due to environmental influences or genetic contributions. A number of environmental influences such as antipsychotic medication, 6 age 7-9 and menstrual phases 10 have been suggested to alter dopamine D2 receptor density. Low dopamine D2 receptor binding in subjects with alcohol, 11,12 cocaine, 13,14 and opiate 15 dependence may suggest that these drugs also have an effect on D2 receptor density. However, the degree to which these factors may alter the receptor density cannot explain the two to threefold variability seen among healthy subjects.1 Animal data suggest a genetic contribution to the variation in dopamine receptor density. Differences in dopamine D2 receptor-binding characteristics between different inbred mice and rat strains have been repeatedly confirmed. [16][17][18][19][20][21][22][23][24] In inbred mice strains a genome-wide search for catalepsy-related genes using a quantitative trait loci approach detected a locus near or at the DRD2.25 Therefore, also in humans several attempts have been performed searching for associations between dopamine D2 receptor polymorphisms and different measures of dopaminergic binding parameters or glucose metabolism in brain regions containing dopaminergic innervation (Table 1).In a recent PET investigation of Finnish healthy individuals the DRD2 TaqIA1 allele, suggeste...

Background:The clinical efficacy of dopamine D 2 receptor antagonism on the psychotic symptoms of schizophrenia has been widely demonstrated. However, most in vivo imaging studies have not been able to detect significant changes in striatal D 2 receptors in schizophrenia. On the other hand, a number of studies have reported abnormalities in the cerebral cortex of schizophrenia. The aim of this study was to examine the extrastriatal D 2 receptors of patients with schizophrenia.Methods: Eleven drug-naive male patients with schizophrenia were examined with positron emission tomography using carbon 11-labeled FLB 457. Symptoms were assessed using the Brief Psychiatric Rating Scale. Eighteen healthy controls were used for comparison. Regionof-interest analysis was performed using the reference tissue method, and binding potential (BP) was used for the index of dopamine D 2 receptor binding.Results: The BP value was significantly lower, by about 12.5%, in the anterior cingulate cortex in drug-naive patients with schizophrenia than in healthy controls. A significant negative correlation was observed between BP in the anterior cingulate cortex and the positive symptom score on Brief Psychiatric Rating Scale. Conclusions:The lower BP values indicate fewer D 2 receptors in the anterior cingulate cortex in patients with schizophrenia. Alterations in D 2 receptor function in the extrastriatal region may underlie the positive symptoms of schizophrenia.

Lead-free ferroelectric K 0:5 Na 0:5 NbO 3 (KNN) thin films have been synthesized by the chemical solution deposition. The optimization of excess amounts of K and Na in KNN precursor solutions was found to be effective for achieving perovskite KNN single-phase thin films with improved leakage current properties. It was revealed from Raman spectroscopic analysis data that a change in scattering mode was observed for the KNN thin films fabricated under various processing conditions. This change was due to the chemical composition fluctuation of K and Na in the KNN thin films after heat treatment. The leakage current and ferroelectric properties of the perovskite KNN thin films were strongly affected by the excess amounts of K and Na as well as the heating conditions of the precursor films. Optimized KNN thin films with 10 mol % excess K and Na exhibited a ferroelectric polarization-electric field (P-E) hysteresis loop with 2P r and 2E c values of 14 mC/cm 2 and 140 kV/ cm, respectively.

We recently developed [11C]FLB 457 a substituted benzamide with the very high affinity of 20 pM for D2-dopamine receptors in vitro. The aim of the present exploratory study was to examine the anatomical distribution of [11C]FLB 457 binding in the human brain and to determine extrastriatal D2-receptor occupancy in antipsychotic drug-treated patients. [11C]raclopride was used to obtain reference values for D2-dopamine receptor occupancy in the putamen. After IV injection of [11C]FLB 457 there was a high concentration of radioactivity, not only in the caudate putamen but also in the thalamus and the temporal cortex. The concentration of radioactivity in the frontal cortex, the substantia nigra and the colliculi was slightly higher than in the cerebellum. Pretreatment with haloperidol and fluphenazine indicated that [11C]FLB 457 binding in extrastriatal regions to a high degree represent specific binding to D2-dopamine receptors. The D2-occupancy in antipsychotic drug-treated patients was on the same level in the thalamus and the temporal cortex as that determined with [11C]raclopride in the putamen. The study shows that [11C]FLB 457 has potential for quantitative PET-examination of D2-dopamine receptors in man.

Lead-free piezoelectric K0.5Na0.5NbO3 thin films for microelectromechanical systems were fabricated via chemical solution process using metal alkoxide. Perovskite K0.5Na0.5NbO3 (KNN) single-phase thin films with good leakage current properties were successfully prepared by optimizing the KxNaxNbO3 (x≧0.5) composition of the precursor solution. The KNN thin films prepared from the solution with K0.55Na0.55NbO3 composition showed typical ferroelectric P–E hysteresis and field-induced strain loops. The 2Pr and 2Ec values of the K0.55Na0.55NbO3 films were 14 µC/cm2 and 140 kV/cm, respectively. From the slope of the field-induced butterfly loop, the effective d33 was found to be 46 pm/V.