Previous neurochemical and behavioural studies show that tyrosine depletion using a nutritionally balanced tyrosine-free amino acid mixture attenuates the dopamine-releasing and psychostimulant properties of amphetamine. Here we investigate the effect of a tyrosine-free amino acid mixture on striatal binding of [(11)C]raclopride, and amphetamine-induced [(11)C]raclopride displacement, using positron emission tomography in the rat. Rats were scanned for 60 min after an i.v. injection of approximately 11 MBq [(11)C]raclopride using a quad-HIDAC system. Amphetamine (2 mg/kg i.p., 30 min prior to scan) caused a 12% reduction in [(11)C]raclopride distribution volume ratio (DVR) compared to saline-injected controls. The tyrosine-free amino acid mixture (1 g/kg i.p.) caused a small (+7%) but statistically insignificant increase in [(11)C]raclopride DVR and attenuated, although it did not fully block, the amphetamine-induced reduction. These data are in keeping with previous neurochemical, immunocytochemical,
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We measured the long-term test-retest reliability of [C-11]raclopride binding in striatal subregions, the thalamus and the cortex using the bolus-plus-infusion method and a high-resolution positron emission scanner. Seven healthy male volunteers underwent two positron emission tomography (PET) [C-11]raclopride assessments, with a 5-week retest interval. D-2/3 receptor availability was quantified as binding potential using the simplified reference tissue model. Absolute variability (VAR) and intraclass correlation coefficient (ICC) values indicated very good reproducibility for the striatum and were 4.5%/0.82, 3.9%/0.83, and 3.9%/0.82, for the caudate nucleus, putamen, and ventral striatum, respectively. Thalamic reliability was also very good, with VAR of 3.7% and ICC of 0.92. Test-retest data for cortical areas showed good to moderate reproducibility (6.1% to 13.1%). Our results are in line with previous test-retest studies of [C-11]raclopride binding in the striatum. A novel finding is the ...
BACKGROUND Quantitative measures of 11C-raclopride receptor binding can be used as a correlate of postsynaptic D2 receptor density in the striatum, allowing 11C-raclopride positron emission tomography (PET) to be used for the differentiation of Parkinsons disease from atypical parkinsonian syndromes. Comparison with reference values is recommended to establish a reliable diagnosis. A PET template specific to raclopride may facilitate direct computation of parametric maps without the need for an additional MR scan, aiding automated image analysis. METHODS Sixteen healthy volunteers underwent a dynamic 11C-raclopride PET and a high-resolution T1-weighted MR scan of the brain. PET data from eight healthy subjects was processed to generate a raclopride-specific PET template normalized to standard space. Subsequently, the data processing based on the PET template was validated against the standard magnetic resonance imaging (MRI)-based method in 8 healthy subjects and 20 patients with suspected ...
Converging evidence from clinical, preclinical, neuroimaging, and genetic research implicates dopamine neurotransmission in the pathophysiology of attention deficit hyperactivity disorder (ADHD). The in vivo neuroreceptor imaging evidence also suggests alterations in the dopamine system in ADHD; however, the nature and behavioral significance of those have not yet been established. Here, we investigated striatal dopaminergic function in ADHD using [(11)C]raclopride PET with a d-amphetamine challenge. We also examined the relationship of striatal dopamine responses to ADHD symptoms and neurocognitive function. A total of 15 treatment-free, noncomorbid adult males with ADHD (age: 29.87 ± 8.65) and 18 healthy male controls (age: 25.44 ± 6.77) underwent two PET scans: one following a lactose placebo and the other following d-amphetamine (0.3 mg/kg, p.o.), administered double blind and in random order counterbalanced across groups. In a separate session without a drug, participants performed a ...
We intend to combine molecular genetics of the dopamine receptors (D2, D3 D4 and D5) and brain imaging using 11 C Raclopride in Positron Emission Tomography (PET). 11 C Raclopride is a ligand which binds to the dopamine receptor D2 and can measure dopamine release during pleasure or anticipatory reward associated with sex. The current proposal will measure changes in DRD2 receptor occupancy using 11 C Raclopride following explicit visual sexual desire cues in healthy control subjects and individuals who suffer from sexual dysfunction. This is in order to determine how individual genotypes modulate dopamine release in vivo in the human brain ...
Our findings that lower income smokers were more likely to have smoking-induced deprivation are consistent with previous findings from a study conducted in developed countries17 and a study conducted in Mexico.18 This emphasises the need to implement tobacco prevention and cessation programmes that specifically target low-income smokers in order to reduce smoking-induced deprivation of household essentials.. Our study also found that smokers residing in Shenyang and Yinchuan were more likely to have smoking-induced deprivation than smokers living in Beijing. This might be because these cities are less economically developed than Beijing.12. We found no statistically significant relationship between smoking intensity and smoking-induced deprivation. This differs from the findings of two previous studies conducted by Siahpush et al.17 One of their studies found that smokers who had higher levels of nicotine dependence had higher odds of smoking-induced deprivation. Our results may differ because ...
Background: In this paper we apply the principal-component analysis filter (Hotelling filter) to reduce noise fromdynamic positron-emission tomography (PET) patient data, for a number of different radio-tracer molecules. Wefurthermore show how preprocessing images with this filter improves parametric images created from suchdynamic sequence.We use zero-mean unit variance normalization, prior to performing a Hotelling filter on the slices of a dynamictime-series. The Scree-plot technique was used to determine which principal components to be rejected in thefilter process. This filter was applied to [11C]-acetate on heart and head-neck tumors, [18F]-FDG on liver tumors andbrain, and [11C]-Raclopride on brain. Simulations of blood and tissue regions with noise properties matched to realPET data, was used to analyze how quantitation and resolution is affected by the Hotelling filter. Summing varyingparts of a 90-frame [18F]-FDG brain scan, we created 9-frame dynamic scans with image statistics ...
BACKGROUND: In this paper we apply the principal-component analysis filter (Hotelling filter) to reduce noise from dynamic positron-emission tomography (PET) patient data, for a number of different radio-tracer molecules. We furthermore show how preprocessing images with this filter improves parametric images created from such dynamic sequence.We use zero-mean unit variance normalization, prior to performing a Hotelling filter on the slices of a dynamic time-series. The Scree-plot technique was used to determine which principal components to be rejected in the filter process. This filter was applied to [11C]-acetate on heart and head-neck tumors, [18F]-FDG on liver tumors and brain, and [11C]-Raclopride on brain. Simulations of blood and tissue regions with noise properties matched to real PET data, was used to analyze how quantitation and resolution is affected by the Hotelling filter. Summing varying parts of a 90-frame [18F]-FDG brain scan, we created 9-frame dynamic scans with image ...
BACKGROUND: Receptor imaging studies have reported increased amphetamine-induced dopamine release in subjects with schizophrenia (SCH) relative to healthy control subjects (HCs). A limitation of these studies, performed with D2/3 antagonist radiotracers, is the failure to provide information about D2/3 receptors configured in a state of high affinity for the agonists (i.e., D2/3 receptors coupled to G proteins [D2/3 HIGH]). The endogenous agonist dopamine binds with preference to D2/3 HIGH receptors relative to D2/3 LOW receptors, making it critical to understand the status of D2/3 HIGH receptors in SCH ...
The study is being performed in order to learn more about AZD3480 (potential as treatment for patients with Alzheimers Disease) and to investigate how much of AZD3480 is bound to the nicotinic receptors in the brain at different concentrations of AZD3480 in blood, as well as to investigate the period of time for this binding ...
0016] In a positron emission tomography (PET) study in healthy subjects using 11C-SCH23390 and 11C-raclopride as D1 and D2 receptor tracers, it was found that Compound (I) induces a D2 receptor occupancy of from 11 to 43% in the putamen when increasing the dose from 2 to 10 mg/day given daily for 18 days. Such level of D2 receptor occupancy is low in comparison with that of currently used antipsychotic drugs, which in general requires a D2 receptor occupancy around or exceeding 50% to be therapeutically effective (Stone J M, Davis J M, Leucht S, Pilowsky L S. Schizophr Bull. 2008 Feb. 26). In the same PET study, it was found that Compound (I) induces a D1 receptor occupancy increase from 32 to 69% in putamen when increasing the dose from 2 to 10 mg/day given daily for 18 days. Such high level of D1 occupancy is not generally seen with current used antipsychotic drugs (Farde L, Nordstrom A L, Wiese F A, Pauli S, Halldin C, Sedvall G. Arch Gen Psychiatry. 1992; 49(7):538-44.). Thus, Compound (I) ...
Motor stereotypies, described as repetitive, topographically invariant and seemingly purposeless behaviours, are common to several developmental and neuropsychiatric disorders. While drug induced stereotypy has been ...
The effect of sigma ligands in MCF-7 and melanoma cells was not due to blockade of dopamine D1 and D2 receptors, serotonin (5-HT2) receptors, N-methyl-D-aspartate (NMDA)/phencyclidine receptors, beta-adrenoceptors or opioid receptors, since 100 microM SCH 23390, raclopride, mianserin, (+)-MK-801, propranolol and 1 microM naloxone respectively, were ineffective ...
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Cannabis as a cause of psychosis: an ecogenetic study linking cannabis-induced dopamine response to psychotic mechanisms and ...
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The data presented here demonstrate that blocking dopaminergic signaling within the BLA either at the D1R with SCH23390 or at the D2R with raclopride prevented the amnesia that normally follows post-reactivation protein synthesis inhibition. Therefore, the CS−sucrose memory, retrieved and behaviorally expressed during the memory reactivation session, did not require protein synthesis in order to restabilize and subsequently persist-consistent with the hypothesis that activity at either D1Rs or D2Rs is required for destabilization of the CS−sucrose memory. That the memorys persistence was independent of protein synthesis cannot be attributed to the parameters of the memory reactivation session, since rats having received intra-amygdala vehicle infusions prior to reactivation were subsequently amnesic at test following post-reactivation administration of the protein synthesis inhibitor anisomycin. Furthermore, nonselective antagonism at dopamine receptors with α-flupenthixol did not block ...
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Viewing of single words produces a cognitively complex mental state in which anticipation, emotional responses, visual perceptual analysis, and activation of orthographic representations are all occurring. Previous PET studies have produced conflicting results, perhaps due to the conflation of these separate processes or the presence of subtle differences in stimulus material and methodology. A PET study of 10 normal individuals was carried out using the bolus H215O intravenous injection technique to examine components of processing of passively viewed words. Subjects viewed blocks of random-letter strings or abstract, concrete, or emotional words (words with positive or negative emotional salience). Baseline conditions were either passive viewing of plus signs or an anticipatory state (viewing plus signs after being warned to expect words or random letters to appear imminently). All words (and to a lesser extent the random letters) produced robust activation of cerebral blood flow in the left ...
Animals exhibiting obsessive and compulsive behaviors that resemble OCD in humans have been used as a tool for elucidating possible genetic influences on the disease, potential treatments, and to better understand the pathology of this behavior in general. While such models are useful, they are also limited; it is unclear whether the behavior is ego dystonic in animals. That is, it is difficult to evaluate whether an animal is aware that its behavior is excessive and unreasonable and whether this awareness is a source of anxiety. One study done by Simon Vermeier used neuroimaging to investigate serotonergic and dopaminergic neurotransmission in 9 dogs with Canine Compulsive Disorder (CCD) to measure the serotonin 2A receptor availability. When compared to the 15 non-compulsive dogs used as a control group, the dogs with CCD were found to have lower receptor availability as well as lower subcortical perfusion and hypothalamic availability. The results of this study provide evidence that there are ...
Boston, Butterworth, Cymbalta loxapac. 42 0. Weismer G, we know we are talking to a master rational- izer and a strategic genius.
Issuu is a digital publishing platform that makes it simple to publish magazines, catalogs, newspapers, books, and more online. Easily share your publications and get them in front of Issuus millions of monthly readers. Title: [email protected] Newsletter Issue 1, Author: CISTIB, Name: [email protected] Newsletter Issue 1, Length: 28 pages, Page: 1, Published: 2014-02-26
OBJECTIVE: The serotonin transporter (5-HTT) is a key target for selective serotonin reuptake inhibitors and may be involved in the pathophysiology of major depression. It is now possible to image 5-HTT directly in the human brain, but results from studies of acutely depressed patients have been inconsistent. The purpose of this study was to determine whether abnormalities in 5-HTT might be present in recovered depressed patients. METHOD: The authors measured the binding potential of 5-HTT using [11C]DASB in conjunction with positron emission tomography (PET) in 24 medication-free, recovered depressed male patients and 20 healthy male comparison subjects. The regional estimates of binding potential were obtained using a metabolite-corrected plasma input function method followed by Logan analysis, with the cerebellum as a reference region. RESULTS: The authors found no significant difference in the binding potential of [11C]DASB between the recovered depressed patients and healthy comparison subjects in
The effects of sodium nitroprusside (SNP), 3-morfolinosydnonimine (SIN-1), or S-nitroso-Nacetylpenicillamine (SNAP), on striatal dopamine release in freely moving rats, were evaluated using microdialysis 1 . When infused (1 mM) for 180 min, both SNP (n=3) and SIN-1 (n=3) increased DA dialysate concentrations (baseline levels 6.73±1.02 and 7.15±1.12 nM, respectively). The SNP-induced DA increase was inhibited by deferoxamine co-infusion, thus suggesting a key role for iron in SNP-induced increases in DA release. SNAP 1 mM 180 min infusion decreased dialysate DA (baseline levels 5.34±0.80 nM, n=3). The decrease was a consequence of SNAP-induced non-enzymatic oxidation of extracellular DA; in fact, the decrease was inhibited by N-acetyl-cysteine or uric acid co-infusion. Both SNP and SNAP greatly decreased dialysate ascorbic acid (AA, baseline values 10.82±2.5 and 8.55±2.62 μM, respectively); on the contrary, SIN-1 did not affect dialysate AA (baseline levels 7.90±0.73 μM). These finding ...
We combined psychopharmacology with neurochemical PET imaging, demonstrating for the first time that dissociable effects of methylphenidate on different aspects of cognition are accompanied by changes in D2/D3 receptor availability in distinct striatal subregions. Significant changes in caudate nucleus accompanied drug-induced changes in reversal learning, whereas significant changes in ventral striatum accompanied drug-induced changes in spatial working memory. Receptor availability reflects an interaction between receptor concentration and extracellular dopamine concentration; dopamine release after drug administration results in radioligand displacement, measurable as reduced binding potential. The findings support the hypothesis that methylphenidate affects different cognitive tasks by modulating distinct fronto-striatal loops with distinct optimal dopamine levels and provide a neurobiological account of within-subject variability in drug effects across different cognitive tasks.. Our data ...
In: Kultas-Ilinsky K, Ilinsky IA, editors. Basal Ganglia and Thalamus in Health and Movement Disorders. New York: Kluwer Academic Plenum Press, pp. 61-67, 2001 Abstract Knowledge of the organization and connections of the basal ganglia has greatly advanced in recent years, and, concurrently, und ...