摘要:

AbstractThis study images dopamine release in response to a neurochemically specific challenge with the psychostimulant drug methylphenidate. Changes in synaptic dopamine induced by methylphenidate were evaluated with positron emission tomography and [11C]raclopride, a D2receptor radioligand that is sensitive to endogenous dopamine. Methylphenidate significantly decreased striatal [11C]raclopride binding. The decrease was variable and was negatively correlated with age. Mood and anxiety at baseline, were also correlated with methylphenidate‐induced DA changes. This strategy provides a tool to investigate the responsiveness of the dopamine system in the normal and diseased human brain and to investigate the neurochemical correlates of behavior. © 1994 Wiley‐Liss,

ISSN:0887-4476    

DOI:10.1002/syn.890160402

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

Abstract[125I]RTI‐55 was used in tracer doses to label serotonin (5‐HT) transporters in vivo in the mouse brain. Fluoxetine, paroxetine, and sertraline, potent antidepressants and selective inhibitors of serotonin transporter sites, were administered in various doses and at various times. The doses and times that result in significant binding of the drugs to transporters correspond to doses and times where they are reported to have physiological effects. Estimates of occupancy rate and duration of binding to serotonin transporters were made. The rate of occupancy of the 5‐HT transporter site was fastest for sertraline, intermediate for paroxetine and slowest for fluoxetine. Similarly, the duration of occupancy was significantly shorter for sertraline and paroxetine (approximately 10 h) than for fluoxetine (approximately 50 h). The results indicate that in competition studies, [125I]RTI‐55 can be used to identify doses of drugs that are physiologically effective, to determine their relative rate of occupancy, and most importantly, to measure the residency time on the central serotonin transporter in vivo. © 1994 Wiley

ISSN:0887-4476    

DOI:10.1002/syn.890160403

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThe role of the striatum in the control of movements and in the processing of cortical information has received much attention in the recent years. We set out a simple biophysical model for the medium‐spiny neuron (msn), the most abundant cell in striatum. This neuron receives two main kinds of inputs, namely, cortical excitatory inputs and dopaminergic inputs coming from the substantia nigra pars compacta. The msn axon impinges directly onto the globus pallidus and onto the substantia nigra pars reticulata neurons and onto striatal neurons through recurrent branches of the axon. The msn is characterized by spiny dendritic trees with a high density of spines (1 to 4 spines/μ) and the probable existence of dendritic spikes. The model predicts that the neuron can integrate excitable inputs in a linear or a nonlinear mode. In the nonlinear mode, the neuron allows the detection of simultaneous (or almost simultaneous) synaptic inputs; it facilitates either a slowing down or a speeding up of the information transfer between the synaptic input location and the soma and is sensitive to inhibition‐excitation pairing. Conversely, in the linear integrative mode, the somatic voltage is determined by a weighted summation of the synaptic inputs. Several geometrical, electrical, or temporal factors can control the switch between these behaviors: the density of excitable dendritic elements, the dendritic radius, the resistance of the spine stem, the membrane resistance, the time between excitations, and the distance between synaptic sites. Finally, the signification of this behavior is discussed in connection with the putative role of dopamine and with the striatal net organization. © 1994 Wiley‐Li

ISSN:0887-4476    

DOI:10.1002/syn.890160404

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

Abstractα1‐Antichymotrypsin (α1‐ACT) is an early‐stage acute‐phase plasma protein and a serpin that preferentially inactivates chymotrypsin, cathepsin G, and chymase. Using immunofluorescence with four rabbit polyclonal and two monoclonal specific antibodies against human α1‐ACT, we have localized α1‐ACT at human and rat neuromuscular junctions (NMJs). Strong α1‐ACT immunoreactivity (IR) was present at all NMJs identified by bound α‐bungarotoxin (α‐BT). α1‐ACT immunoreactivity typically extended slightly deeper into the muscle fiber than α‐BT, and it closely co‐localized with immunoreactivities of post‐synaptic desmin, beta‐amyloid precursor protein, and dystrophin at the same double‐ or triple‐labeled NMJs. Topography of α1‐ACT‐IR was the same at human and rat NMJs. The muscle non junctional sarcolemma was either not immunoreactive or was only very slightly so. When the primary antibody was omitted, absorbed, or replaced by a non‐immune serum, there was no immunostaining. Thus, αl‐ACT is a novel component of the NMJ. Although its role in the postsynaptic domain of the NMJ is unknown, it might be involved in the interaction between the presynaptic and postsynaptic components and/or inhibit excessive or unwanted serine proteases that may exis

ISSN:0887-4476    

DOI:10.1002/syn.890160405

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractA neglected type of neuron, termed theunipolar brush cell, was recently characterized in the granular layer of the mammalian cerebellar cortex with several procedures, including light and electron microscopic immunocytochemistry utilizing antibodies to calretinin and neurofilament proteins. Although certain features of the unipolar brush cells were highlighted in these studies, the internal fine structure was partially obfuscated by immunoreaction product. In this study, rat cerebella were prepared for electron microscopy after perfusion fixation and Araldite embedding, and folia of the vestibulo‐cerebellum, where unipolar brush cells are known to be enriched, were studied by light microscopy in semithin (0.5–1 μ) sections and by electron microscopy in ultrathin sections. Unipolar brush cells were easily identified in semithin sections immunostained with antibodies to GABA and/or glycine, and cbunterstained with toluidine blue. The unipolar brush cells have a pale cytoplasm and are GABA and glycine negative, while Golgi cells are darker and appear positive for GABA and, for the most part, also for glycine. Sets of identification criteria to differentiate unipolar brush cells from granule and Golgi cells in standard electron micrographs are presented. The unipolar brush cells possess many distinctive features that make them easily distinguishable from other cerebellar neurons and form unusually conspicuous and elaborate synapses with mossy rosettes. The unipolar brush cell has a deeply indented nucleus containing little condensed chromatin. The Golgi apparatus is large and the cytoplasm is rich in neurofilaments, microtubules, mitochondria, and large dense core vesicles, but contains few cisterns of granular endoplasmic reticulum. In addition, unipolar brush cells contain an unusual inclusion, which invariably lacks a limiting membrane and is made up of peculiar ringlet subunits. The cell body usually emits a thin axon and is provided with a single, large dendritic trunk that terminates with a paintbrush‐like bunch of branchlets. Numerous nonsynaptic appendages emanate from the cell body, the dendritic stem, and the branchlets. The appendages contain rare organelles and lack neurofilaments. The branchlets contain numerous mitochondria, neurofilaments, large dense core vesicles, and clusters of clear, small, and round synaptic vesicles. They form extensive asymmetric synaptic junctions with of a or two mossy fibers, which indicates minimal convergence of excitatory inputs. Under the postsynaptic densities, the branchlet cytoplasm displays a microfilamentous web. Besides their contact with mossy rosettes, the branchlets form symmetric and asymmetric synaptic junctions with presumed Golgi cell boutons that contain pleomorphic synaptic vesicles, indicating that the unipolar brush cells receive an inhibitory modulation. Some of these junctions are unusually extensive. The branchlets also form asymmetric synapses with granule cell dendrites, in which they represent the presynaptic elements, a feature never described before in the normal cerebellum. A minority of the unipolar brush cells receive mossy fiber contacts directly on the cell body, or on short dendritic branchlets emanating directly from the cell body. Such “enmarron” synapses were previously attributed to Golgi cells. Thus, the unipolar brush cells have complex synaptic features: Besides being specialized to form a powerful link with mossy rosettes, they may also have a paracrine function, and they participate with presynaptic dendrites in the cerebellar microcircuit. © 1994 Wile

ISSN:0887-4476    

DOI:10.1002/syn.890160406

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractPositron emission tomography (PET), [11C]cocaine, and (–)‐6‐[18F]fluoronorepinephrine [(‐)‐6‐[18F]NE]were used to determine the extent to which the binding of labeled cocaine in the baboon heart represents binding to the norepinephrine transporter and to characterize the functional consequences of cocaine administration on the norepinephrine transporter. Peak heart binding of [11C] cocaine was high (0.038‐0.055%/g) and clearance was rapid (t1/2from peak: 2.5–9 min) for both tracer doses and a pharmacological dose. The binding of a tracer dose of labeled cocaine could not be inhibited by desipramine, tomoxetine, cocaine, nomifensine, or benztropine. The behavior of a pharmacological dose of [11C]cocaine could not be distinguished from a tracer dose and also could not be inhibited by tomoxetine. However, pretreatment with cocaine profoundly inhibited norepinephrine uptake as assessed by (–)‐6‐[18F]NE. Recovery was slow with only 48% of the baseline (–)‐6‐[18F]NE uptake being recovered by 78 minutes after cocaine administration. [11C]Benzoylecgonine, a vasoactive metabolite of cocaine, showed negligible retention in heart. The results of this study (i.e., the rapid clearance of cocaine from the heart, the inability to inhibit cocaine binding with desipramine and tomoxetine, and its relatively long‐lasting effects on norepinephrine uptake) reinforce the need to understand the link between cocaine pharmacokinetics and norepinephrine transporter function and its relationship to cardiotox

ISSN:0887-4476    

DOI:10.1002/syn.890160407

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

ISSN:0887-4476    

DOI:10.1002/syn.890160401

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY