89 research outputs found
D1 dopamine receptor immunoreactivity in human and monkey cerebral cortex: predominant and extrasynaptic localization in dendritic spines.
The striatal dopamine transporter in first-episode, drug-naive schizophrenic patients: evaluation by the new SPECT-ligand[99mTc]TRODAT-1
Following the current hypothesis that acute schizophrenic psychotic illness is associated with a triatal ‘hyperdopaminergic state’, presynaptic integrity and dopamine transporter (DAT) density in first-episode, neuroleptic-naive schizophrenic patients was measured by single-photonemission- tomography (SPECT) and compared with that in healthy control subjects. A new SPECT-ligand for assessment of the striatal DAT, the Technetium-99m-labelled tropane TRODAT-1 ([99mTc]TRODAT-1), was used. Ten inpatients suffering from a first acute schizophrenic episode and 10 age- and sex-matched healthy control subjects underwent SPECT with [99mTc]TRODAT-1. On the day of SPECT, psychopathological ratings were performed with the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS) and Schedule for Assessment of Negative Symptoms (SANS). Patients had not previously received any neuroleptic or antidepressant medication. Mean specific TRODAT-1 binding in the striatum did not differ significantly between the patient and the age- and sex-matched control group (1.25 vs. 1.28). Variance was significantly higher in the patient group. The data obtained with the new ligand in first-episode, drug-naive schizophrenic patients are in line with the PET results from the group of Laakso et al. in a comparable patient sample. [99mTc]TRODAT-1 seems to be a valuable new SPECTligand in the evaluation of the presynaptic site of the striatal dopaminergic synapse in schizophrenia
In vivo [3H]flunitrazepam binding: imaging of receptor regulation
ABSTRACT ABBREVIATIONS: BDZ, benzodiazepine; GABA, 'y-aminobutyric acid; HO, Huntington's Disease; GP, globus pallidus; SNr, substantia nigra pars reticulata; FLU, flunitrazepam; PET, positron emission tomography; BBB, blood-brain barrier. 74
NMDA receptor channels: Labeling of MK-801 with iodine-125 and fluorine-18
Methods for labeling the glutamate channel blocking agent MK-801 with iodine-125 (125I) and fluorine-18 (18F) are described. Radioiodine was incorporated in the 1- or 3-positions of the aromatic ring of (+/-)MK-801 by solid-state halogen exchange techniques. Attachment of the [18F]fluoromethyl group to the bridgehead methyl position was achieved by reaction of [18F]fluoride with the triflamide alcohol 8 or the novel cyclic sulfamate 9 recently reported by Merck chemists. Radiochemical yields of (+/-)13-[18F]- fluoromethyl-MK-801 were >72%, EOB; radiochemical purity >99%. In competitive binding studies using rat brain homogenates, (+/-)3-bromo-MK-801 showed greater affinity than (+/-)MK-801 for the glutamate-linked channel. The experimental log P (2.1 +/- 0.1) of MK-801 is optimal for transit of the blood-brain barrier. These preliminary findings support further testing of 3-[123I]iodo-MK-801 and (+/-)13-[18F]fluoromethyl-MK-801 as possible agents for in vivo mapping of the glutamate receptor complex.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27605/1/0000649.pd
Imaging the Dopamine Uptake Site with Ex Vivo [ 18 F]GBR 13119 Binding Autoradiography in Rat Brain
We studied the binding of [ 18 F]GBR 13119 {1-[[(4-[ 18 F]fluorophenyl) (phenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine} to rat brain with autoradiography after intravenous injection. The rank order of binding was dorsal striatum > nucleus accumbens = olfactory tubercle > sub-stantia nigra = ventral tegmental area > other areas. Binding was blocked by prior injection of dopamine uptake blockers but not by injection of dopamine receptor antagonists or drugs that bind to the dialkylpiperazine site. Unilateral 6-hydroxy dopamine lesions of dopamine neurons caused a marked decrease in striatal and nigral binding on the side of the lesion. We conclude that intravenous injection of [ 18 F]GBR 13119 provides a useful marker of presynaptic dopamine uptake sites.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66209/1/j.1471-4159.1990.tb04178.x.pd
Quantitative in vivo receptor binding IV: Detection of muscarinic receptor down-regulation by equilibrium and by tracer kinetic methods
Newly-developed methods for estimation of in vivo binding to neurotransmitter receptors should enable the detection and quantification of physiologic or pathologic changes in receptor numbers. In the present study, both equilibrium and kinetic experimental strategies for in vivo muscarinic receptor determination were applied to the detection of receptor changes induced by chronic inhibition of acetylcholinesterase in the rat. Following one week of treatment, in vitro receptor autoradiography utilizing [ 3 H]scopolamine revealed significant losses of muscarinic binding in the cerebral cortex, hippocampus, striatum and in cranial nerve motor nuclei. The in vivo distribution of [ 3 H]scopolamine, following infusion to approach equilibrium binding in the brain, revealed reductions in binding which paralleled the pattern and magnitude of changes detected in vitro. A simplified tracer kinetic estimation following bolus injection of the ligand also detected substantial reductions in forebrain muscarinic receptor binding. These results indicate the feasibility of detecting receptor changes underlying neuropathologic conditions in vivo, and suggest that either equilibrium or kinetic experimental approaches may be extended to clinical research applications with the use of positron or single-photon emission tomography.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45405/1/11064_2004_Article_BF00965845.pd
Neuroanatomical Study of the A11 Diencephalospinal Pathway in the Non-Human Primate
BACKGROUND: The A11 diencephalospinal pathway is crucial for sensorimotor integration and pain control at the spinal cord level. When disrupted, it is thought to be involved in numerous painful conditions such as restless legs syndrome and migraine. Its anatomical organization, however, remains largely unknown in the non-human primate (NHP). We therefore characterized the anatomy of this pathway in the NHP. METHODS AND FINDINGS: In situ hybridization of spinal dopamine receptors showed that D1 receptor mRNA is absent while D2 and D5 receptor mRNAs are mainly expressed in the dorsal horn and D3 receptor mRNA in both the dorsal and ventral horns. Unilateral injections of the retrograde tracer Fluoro-Gold (FG) into the cervical spinal enlargement labeled A11 hypothalamic neurons quasi-exclusively among dopamine areas. Detailed immunohistochemical analysis suggested that these FG-labeled A11 neurons are tyrosine hydroxylase-positive but dopa-decarboxylase and dopamine transporter-negative, suggestive of a L-DOPAergic nucleus. Stereological cell count of A11 neurons revealed that this group is composed by 4002±501 neurons per side. A 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) intoxication with subsequent development of a parkinsonian syndrome produced a 50% neuronal cell loss in the A11 group. CONCLUSION: The diencephalic A11 area could be the major source of L-DOPA in the NHP spinal cord, where it may play a role in the modulation of sensorimotor integration through D2 and D3 receptors either directly or indirectly via dopamine formation in spinal dopa-decarboxylase-positives cells
A 40-bp VNTR polymorphism in the 3′-untranslated region of DAT1/SLC6A3 is associated with ADHD but not with alcoholism
GABA and benzodiazepine receptors in basal ganglia function
GABA and its associated benzodiazepine interactions play an important role in basal ganglia function. Distinctive GABA, benzodiazepine and opiate receptor changes occur in response to striatal lesions and in the human neurodegenerative disorder, Huntington's disease (HD). In animal experiments, the in vivo administration of [3H]flunitrazepam labels benzodiazepine receptors and can demonstrate the receptor changes seen after striatal lesions. It should be possible to measure these receptors in vivo in humans using positron-emission tomographic scanning.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24774/1/0000198.pd
- …