bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of striatal histamine H2 receptors in Huntington's: Chorea but not in Parkinson's disease: Comparison with animal models
Authors: Martínez‐Mir M. I. , Pollard H. , Moreau J. , Traiffort E. , Ruat M. , Schwartz J. C. , Palacios J. M. 
Published: December 2004

AbstractAutoradiographic techniques were used to study the distribution of histamine H2‐receptors as labeled with [125I]iodoaminopotentidine in the brains of patients affected by human neurodegenerative pathologies, as compared with control cases. The highest levels of histamine H2 binding sites in control cases were found in the caudate, putamen, and accumbens nuclei. In Huntington's chorea, the levels of histamine H2 receptor binding sites were found to be markedly decreased in virtually all regions examined, particularly in the putamen and globus pallidus lateralis. The loss of binding sites was related to the grade of the disease. Losses were more marked in grade III disease cases. The possible influence of neuroleptic treatment, commonly used in Huntington's patients, was studied by including samples from clinically treated schizophrenic patients. A moderate increase in the densities of [125I]iodoaminopotentidine was found in the globus pallidus of these patients. In Parkinson's disease, the levels of histamine H2‐receptor binding sites were found not to be significantly different from those of control cases. These results were comparable with those obtained from unilaterally neurotoxin‐lesioned guinea pigs. Similar losses of binding sites were observed in the quinolinic acid lesioned striatal intrinsic neurons in the guinea pig, whereas lesioning dopaminergic cell bodies in the substantia nigra with 6‐hydroxydopamine did not produce any significant change. These results strongly suggest that histamine H2‐receptors are expressed by striatal neurons, which degenerate in Huntington's chorea, but not by nigral dopaminergic neurons and may play a role in the regulation of the intact striato‐nigral pathway. © 1993 Wiley‐Liss, Inc.
GABAB‐Receptor activation alters the firing pattern of dopamine neurons in the rat substantia nigra
Authors: Engberg Göran , Kling‐Petersen Torben , Nissbrandt Hans 
Published: December 2004

AbstractPrevious electrophysiological experiments have emphasized the importance of the firing pattern for the functioning of midbrain dopamine (DA) neurons. In this regard, excitatory amino acid receptors appear to constitute an important modulatory control mechanism. In the present study, extracellular recording techniques were used to investigate the significance of GABAB‐receptor activation for the firing properties of DA neurons in the substantia nigra (SN) in the rat. Intravenous administration of the GABAB‐receptor agonist baclofen (1–16 mg/kg) was associated with a dose‐dependent regularisation of the firing pattern, concomitant with a reduction in burst firing. At higher doses (16–32 mg/kg), the firing rate of the DA neurons was dose‐dependently decreased. Also, microiontophoretic application of baclofen regularized the firing pattern of nigral DA neurons, including a reduction of burst firing. Both the regularisation of the firing pattern and inhibition of firing rate produced by systemic baclofen administration was antagonized by the GABAB‐receptor antagonist CGP 35348 (200 mg/kg, l.v.). The GABAA‐receptor agonist muscimol produced effects on the firing properties of DA neurons that were opposite to those observed following baclofen, i.e., an increase in firing rate accompanied by a Cecreased regularity. The NMDA receptor antagonist MK 801 (0.4–3.2 mg/kg, i.v.) produced a moderate, dose‐dependent increase in the firing rate of the nigral DA neurons as well as a slightly regularized firing pattern. Pretreatment with MK 801 (3.2 mg/kg, i.v., 3–10 min) did neither promote nor prevent the regularisation of the firing pattern or inhibition of firing rate on the nigral DA neurons produced by baclofen. The present results clearly show that GABAB‐receptors can alter the firing pattern of nigral DA neurons, hereby counterbalancing the previously described ability of glutamate to induce burst Firing activity on these neurons. © 1993 Wiley‐Liss, Inc.
Time‐dependent changes in sensitivity to apomorphine and monoamine receptors following withdrawal from continuous cocaine administration in rats
Authors: Neisewander Janet L. , Lucki Irwin , McGonigle Paul 
Published: December 2004

AbstractThe effects of withdrawal from continuous administration of cocaine on behavioral sensitivity to apomorphine and monoamine receptor density were examined in rats. Subdermal minipumps that delivered either saline or 20 mg/kg/day cocaine hydrochloride were implanted for 2 weeks. Apomorphine‐induced stereotypy (0.5 mg/kg, SC) was examined in separate groups of rats either 4 hr or 7, 28, or 60 days after removal of the minipumps. Transient enhanced sensitivity to apomorphine‐induced stereotypy occurred during the course of withdrawal. Animals withdrawn from cocaine for 4 hours did not differ from controls in their sensitivity to apomorphine, whereas animals withdrawn from cocaine for 7 days exhibited an increase in apomorphine‐induced oral stereotypy relative to controls. However, the enhanced stereotypy response was no longer evident in animals withdrawn for 28–60 days. The animals were sacrificed after behavioral testing, and their brains were assayed for changes in monoamine receptor density in the frontal cortex, caudate‐putamen, and nucleus accumbens. The density of 3H‐SCH‐23390‐labeled D1 receptors was altered in all three regions examined in a time‐dependent manner that paralleled the changes in behavioral sensitivity to apomorphine. There was a transient decrease in D1 receptor density that was evident by 7 days following withdrawal from continuous cocaine administration and was no longer evident 28 or 60 days posttreatment. There were no changes in 3H‐spiroperidol‐labeled D2 receptors, 125‐pindolol‐labeled β‐adrenergic receptors, or 3H‐ketanserin‐labeled 5‐HT2 receptors in any of the regions examined at both 4 hr and 7 days after termination of the cocaine infusion. These findings are discussed in terms of their relevance to developing pharmacologic treatments for withdrawal from cocaine. © 1994 Wiley‐Liss, Inc.
Power spectral analysis of electroencephalographic desynchronization induced by cocaine in rats: Correlation with microdialysis evaluation of dopaminergic neurotransmission at the medial prefrontal cortex
Authors: Luoh Hsiang‐Fei , Kuo Terry B. J. , Chan Samuel H. H. , Pan Wynn H. T. 
Published: December 2004

AbstractWe evaluated the effect and action mechanisms of cocaine on electroencephalographic (EEG) activity in adult male Sprague‐Dawley rats anesthetized with chloral hydrate (400 mg/kg, i.p., with 80 mg/kg/h supplements). On‐line and real‐time power spectral analysis of the EEG activity continuously quantified its root mean square (RMS) and mean power frequency (MPF) values, and the power of its spectral frequency components (low frequency: 0–4 Hz; high frequency: 4–20 Hz). Administration of cocaine (1.5 or 3.0 mg/kg, i.v.) dose‐dependently induced EEG desynchronization, as manifested by a reduction in RMS and an elevation in MPF values, coupled with a differential decrease in both high and low frequency components. Samples collected by in vivo microdialysis at the medial prefrontal cortex (mPFC) and analyzed by HPLC showed that the elevation of cocaine and dopamine (DA) level in the dialysate reached its peak during the time interval when maximal activation of EEG occurred. This EEG activation was antagonized by microinfusion into the mPFC via reverse microdialysis of R(+)‐SCH 23390, a selective antagonist for D‐1 receptors; sulpiride, a selective antagonist for D‐2 receptors; or haloperidol, a nonspecific dopamine antagonist. These results suggest that dopaminergic neurotran:3mission at the mPFC may be intimately related to the specific spectral pattern of alteration in EEG activity elicited by cocaine in the rat and that both D‐1 and D‐2 receptors may be involved in the process. © 1994 Wiley‐Liss, Inc.
Gene expression in central cholinergic neurons in response to axotomy and deafferentation
Authors: Weiser Michael , Baker Harriet , Joh Tong H. 
Published: December 2004

AbstractAlthough the molecular and cellular responses to injury in the central nervous system (CNS) have been widely investigated, few studies have examined the potential variations between direct and indirect neuronal injury. To differentiate between the response to axotomy and deafferentation, two central cholinergic populations were analyzed: the horizontal limb of the diagonal band of Broca (HLDB) and the interneurons in the corpus striatum (CS). At time points from one hour to eight weeks postinjury the levels of choline acetyltransferase (ChAT) mRNA and protein were assessed by in situ hybridization and immunohistochemistry. Also examined was the expression of the immediate early gene product, c‐fos. One week post axotomy, neurons in the HLDB exhibited an increase in the levels of ChAT mRNA without a concomitant increase in ChAT protein, followed by a steady decrease reaching a nadir in both parameters at eight weeks. In contrast, a transient increase occurred at one week postdeafferentation in the levels of both ChAT mRNA and protein in the interneurons of the CS. Axotomized neurons in the HLDB did not exhibit either c‐fos mRNA or protein expression, while robust fos induction occurred after one hour in deafferented neurons in the CS. These data demonstrate that the molecular and cellular responses differ following direct and indirect neufenal injury. Furthermore, they suggest that in these central cholinergic populations deafferentation may result in cellular hyperactivity and cell survival while axotomy, results in decreased cellular activity and subsequent cellular regression. © 1994 Wiley‐Liss, Inc.
Desensitization and noncompetitive blockade of GABAA receptors in ventral midbrain neurons by a neurosteroid dehydroepiandrosterone sulfate
Authors: Spivak Charles E. 
Published: December 2004

AbstractDehydroepiandrosterone sulfate (DHEAS) blocked the GABAA receptor noncompetitively in neurons grown in primary culture from the ventral midbrains of fetal rats. The apparent dissociation constant for this blockade was 4.5 μ, and one molecule of DHEAS was sufficient to block the receptor. The affinity of the blocked receptor for GABA was diminished by about one half. The findings that the DHEAS caused no rectification of chloride currents and that it did not shorten the durations of open ion channels indicated that DHEAS did not act by occluding open ion channels. Neither did it diminish their conductance. DHEAS accelerated desensitization in at least one population of receptors, diminished the amplitudes of inhibitory postsynaptic currents, and shortened their decay time constants in a concentration dependent manner. © 1994 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.
Modulation of cellular excitability in neocortex: Muscarinic receptor and second messenger‐mediated actions of acetylcholine
Authors: Cox Charles L. , Metherate Raju , Ashe John H. 
Published: December 2004

AbstractMuscarinic‐type acetylcholine (ACh) receptors are involved in a variety of cortical functions. ACh “activates” neocortex; simultaneously modifying spontaneous subthreshold activity, intrinsic neuronal oscillations and spike discharge modes, and responsiveness to fast (putative glutamatergic) synaptic inputs. However, beyond the general involvement of muscarinic receptors, a mechanistic understanding of integrated cholinergic actions, and interactions with non‐cholinergic transmission, is lacking. We have addressed this problem using intracellular recordings from the in vitro auditory neocortex. First, we investigated cholinergic modification of responses to the excitatory amino acid glutamate. ACh, or the muscarinic agonist methacholine, produced a lasting enhancement of glutamate‐mediated membrane depolarizations. Muscarinic receptors of the M1and/or M3subtype, rather than M2or nicotinic receptors, mediated this enhancement. Subsequently, we investigated whether second messenger systems contribute to observed muscarinic actions. Activation of protein kinase C with phorbol 12,13‐dibutyrate (4 β‐PDBu), enhanced neuronal responses to glutamate. The effect of 4 β‐PDBu was attenuated by the kinase antagonist H7. Finally, we attempted to identify postsynaptic actions ofendogenousACh. Tetanic stimulation of cholinergic afferents elicited voltage‐dependent effects, including reduced spike frequency adaptation and reduced slow afterhyperpolarization (sAHP) elicited by transmembrane depolarizing stimuli. These effects were mimicked by methacholine, enhanced by eserine, and antagonized by muscarinic receptor antagonists. These data suggest that cholinergic modulation in neocortex likely involves the integrated actions of diverse mechanisms, primarily gated by muscarinic receptors, and at least partly involving second messenger systems. © 1994 Wiley‐Liss, Inc.
Divergence of hippocampal mossy fibers
Authors: Frotscher M. , Soriano E. , Misgeld U. 
Published: December 2004

AbstractBy connecting the fascia dentata with the hippocampus proper, the axons of the granule cells, the mossy fibers, represent an important element of the main excitatory, trisynaptic pathway of the hippocampal formation. In this review the various synaptic connections of the mossy fibers are discussed. It turns out that the mossy fibers do not only establish synapses with the pyramidal neurons of regio inferior as traditionally assumed, but a variety of local circuit neurons as well as projection cells are also contacted by the mossy fibers. Thus there is an underestimated divergence of the impulse flow within the “trisynaptic” pathway at the level of the mossy fibers. Similarly, the pattern of afferent input to the granule cells, especially that of GABAergic neurons, is more complex than previously assumed. In this respect the concept of a unidirectional “trisynaptic” pathway certainly is an oversimplification. In particular, the hilus of the fascia dentata, that the 'mossy fibers traverse on their way to regio inferior, is often neglected in this concept. The hilar region comprises a large variety of morphologically and functionally distinct neuronal types that, to a large extent, are targets of hilar mossy fiber collaterals. By focusing on the mossy fiber system, an attempt is made in this review to summarize new data on hippocampal circuitries that have been accumulated since the original description of the trisynaptic pathway. This concept, which originally comprised the synapses of the perferant path fibers on dentate granule cells, the mossy fiber synapses on CA3 pyramidal neurons, and the synapses of the Schaffer collaterals on CA1 pyramidal cells, has been of great heuristic value but needs to be modified in view of recent morphological and physiological data. © 1994 Wiley‐Liss, Inc.
Mercuric chloride and p‐chloromercuriphenylsulfonate exert a biphasic effect on the binding of the stimulant [3H]methylphenidate to the dopamine transporter
Authors: Schweri M. M. 
Published: December 2004

AbstractMercuric chloride was found to have a biphasic effect on the binding of the radiolabeled stimulant [3H]methylphenidate to membranes from a crude synaptosomal preparation of rat striatal tissue. Binding was enhanced at low concentrations of HgCl2, reaching a maximum of 62% above control values at 2.5 μ HgCl2. It was inhibited in a dose‐dependent manner at concentrations greater than 5 μ HgC12, with an IC50 of 7.2 μ. The increase in binding observed at the low concentrations of HgC12 was shown by Scatchard analysis to be due to an increase in the affinity of [3H]methylphenidate for its binding site on the dopamine transporter, while a decrease in both affinity and Bmax accompanied the reduction of [3H]methylphenidate binding observed at the higher concentrations of the inorganic mercury compound. The sodium salt of the organic mercurial p‐chloromercuriphenylsulfonic acid also caused an increase in [3H]methylphenidate binding (159% above controls at 2,000 μ), followed by an immediate decrease in binding at higher concentrations of the reagent. Because both of these mercury‐containing compounds have a high propensity for interacting with sulfhydryl groups, these data suggest that the cysteine residues in the dopamine transporter molecule may play an important role in the regulation of stimulant binding to the uptake complex. © 1994 Wiley‐Liss, Inc.
Effects of supplemental choline on extracellular acetylcholine in the nucleus accumbens during normal behavior and pharmacological acetylcholine depletion
Authors: Rada Pedro V. , Mark Gregory P. , Hoebel Bartley G. 
Published: December 2004

AbstractBrain microdialysis was used to determine whether systemic or local application of choline would modify the extracellular concentration of acetylcholine (ACh) in the nucleus accumbens (NAc) of freely moving rats. Supplemental choline given intraperitoneally or into the NAc of normal rats did not increase extracellular ACh. When local ACh interneurons in the NAc were treated pharmacologically to deplete the intracellular stores of ACh, then systemic choline (80 mg/kg) was an effective treatment. Specifically, )1) blockade of the high‐affinity choline transporter with hemicholinium‐3 (HC‐3) to reduce ACh synthesis caused a decrease in extracellular ACh, but choline supplementation restored ACh toward its normal level in the NAc. (2) Local bicuculline treatment released ACh to the point of depletion, but systemic choline or locally infused choline helped maintain normal ACh levels. These results suggest that choline supplementation might be useful in preventing depletion of ACh in the nucleus accumbens during pathological conditions. © 1994 Wiley‐Liss, Inc.
Occupancy of the serotonin transporter by fluoxetine, paroxetine, and sertraline: In vivo studies with [125i]rti‐55
Authors: Scheffel Ursula , Kim Stanley , Cline Elizabeth J. , Kuhar Michael J. 
Published: December 2004

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‐Liss, Inc.
Modeling the integrative properties of dendrites: Application to the striatal spiny neuron
Authors: Martiel Jean‐Louis , Mouchet Patrick , Boissier Marie‐Dominique 
Published: December 2004

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‐Liss, Inc.
Alpha 1‐antichymotrypsin is strongly immunolocalized at normal human and rat neuromuscular junctions
Authors: Bilak Masako , Askanas Valerie , Engel W. King 
Published: December 2004

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 exist in the region of the NMJ. © 1994 Wiley‐Liss, Inc.