bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influx of a choline analog to dog brain measured by positron emission tomography
Authors: Redies Christoph , Diksic Mirko , Collier Brian , Gjedde Albert , Thompson Christopher J. , Gauthier Serge , Feindel William H. 
Published: January 2005

AbstractThe influx of the 11C‐labeled choline analog pyrrolidinocholine into tissue was measured in the brain of three dogs by positron emission tomography (PET). During the first 90 s after the intravenous bolus injection of the tracer, transfer of tracer from plasma to tissue was unidirectional. The influx constant for pyrrolidinocholine into intracranial tissue, Kin, was 0.017 ml/g/min (0.008 SD), and the initial volume of distribution, V0, was 0.08 ml/g (0.03 SD). The influx constant was at least five times larger than the value expected if simple diffusion were to account for tissue uptake. The method presented in this paper can be used to investigate the availability of plasma choline and its analogs to the living human brain and other tissue in degenerative diseases affecting the cholinergic system, and to provide in vivo information on a choline transport system.
Effect of agonist concentration on the lifetime of GABA‐activated membrane channels in spinal cord neurons
Authors: Mathers David Alexander , Wang Yihong 
Published: January 2005

AbstractThe inhibitory neurotransmitter γ‐aminobutyric acid (GABA) hyperpolarizes spinal neurons by activating bicuculline sensitive GABAA receptors coupled to chloride permeable ionic channels in the cell membrane. Single channel measurements using outside‐out membrane patches from cultured mouse spinal neurons showed that there is a large excess of brief openings of these channels, compared to the number predicted from a simple, two‐state model of channel function. The cumulative open time distributions for channel openings were well fit by the sum of two exponential terms, a fast component with amplitude Nf and time constant TAUf, and a slow term with amplitude Ns and time constant TAUs. These kinetics could arise if monoliganded GABAA receptors triggered an open state less stable than that induced by the biliganded receptor. A prediction of this hypothesis is that the ratio Nf/Ns should decline in an approximately linear fashion with increasing doses of GABA. This was found to be the case, as Nf/Ns declined by a factor of 4.8 on increasing the GABA dose from 0.5 μM to 5 μM. Application of 1.25 μM GABA produced an intermediate value of Nf/Ns, as predicted. In contrast the parameters TAUf and TAUs were not significantly influenced by GABA concentration. Spontaneous, bicuculline sensitive currents were seen in some patches. These events resembled currents triggered by low doses of exogenous GABA, with regard to the values of Nf/Ns, TAUf and TAUs. These results suggest that the spontaneous currents are triggered by endogenous GABA molecules, present in the culture environment at a concentration of 0.5 μM or less.
Effects of chronic treatment with selective and nonselective antagonists on the subtypes of dopamine receptors
Authors: McGonigle Paul , Boyson Sally J. , Reuter Susan , Molinoff Perry B. 
Published: January 2005

AbstractThe effects of chronic blockade of D‐1, D‐2, or both subtypes of dopamine receptors on the densities and properties of the D‐1 and D‐2 subtypes of dopamine receptors were measured in rat brain. Animals were treated with 14 daily injections (i.p.) of the D‐1‐selective antagonist SCH‐23390, the D‐2‐selective antagonist sulpiride, the nonselective antagonist fluphenazine, or vehicle. Serial 32‐μm horizontal sections that included the caudate putamen were cut and alternately assigned to assays for D‐1 or D‐2 receptors. D‐1 receptors were labeled with 3H‐SKF‐83566 or 3H‐SCH‐23390, and D‐2 receptors were labeled with 3H‐spiroperidol. Scatchard analysis was performed on the saturation data measured in the head of the caudate putamen to obtain estimates of receptor density. As expected, administration of the D‐1‐selective ligand SCH‐23390 resulted in an increase in the density of D‐1 receptors by approximately 47% and had no significant effect on the density of D‐2 receptors. Similarly, administration of the D‐2‐selective ligand sulpiride resulted in an increase in the density of D‐2 receptors by 25% and had no significant effect on the density of D‐1 receptors. Thus the subtypes of dopamine receptors appear to be independently regulated after selective blockade. In contrast to the effects observed with selective antagonists, the results obtained with fluphenazine were more complex. Administration of the relatively nonselective antagonist fluphenazine resulted in an increase in the density of D‐2 receptors by 51% but had no significant effect on the density of D‐1 receptors. One explanation for this result is that up‐regulation of D‐2 receptors inhibits the regulation of D‐1 receptors, suggesting that the regulation of subtypes of dopamine receptors is not entirely independent. In support of this hypothesis, coadministration of sulpiride with SCH‐23390 attenuated the ability of SCH‐23390 to up‐regulate D‐1 receptors. To determine whether this phenomenon is observed in other brain regions, a second group of animals was chronically treated with selective and nonselective antagonists as described above, and coronal sections were cut at multiple levels of the brain. Receptors were labeled with a single concentration of either 3H‐SCH‐23390 or 3H‐spiroperidol, and the binding of the radioligands in 19 discrete brain regions was measured. The effects of these treatments on D‐1 and D‐2 receptors in most of these regions were similar to those described above for the caudate putamen.
In vivo quantification of blood‐brain transfer and binding of [125I]HEAT, an α1‐adrenoceptor antagonist
Authors: Dyve Suzan , Gjedde Albert , Diksic Mirko , Sherwin Allan , Hakim Antoine 
Published: January 2005

AbstractThe uptake and binding constants of [125I]iodo‐2‐[β‐(4‐hydroxyphenyl)‐ethyl‐amino‐methyl]tetralone ([125I]HEAT) in rat brain were determined in vivo. The initial clearance of the radioligand from blood to brain, K1, was calculated from the initial uptake of the radioligand; it averaged 0.21 ± 0.01 (SD) ml g−1 min −1, consistent with an initial extraction of 25% (i.e., one‐quarter of the blood flow). The most strongly binding regions included the olfactory bulb, thalamic nuclei, medial geniculate body, and cerebral cortical layers. We identified saturable, specific binding in frontal cortex layers 1, 5a, and 5c (motor region), frontal cortex layers 3 + 4, ventral thalamic nuclei, medial geniculate body, striatum, cerebellum, and olfactory bulb. Addition of unlabeled ligand depressed binding in all regions to the same low level (partition coefficient) of 0.8 ml g−1. Displacement of [125I]HEAT binding by unlabeled HEAT yielded a global affinity constant (KDVd) of 34 ± 8 pmol g−1 and receptor densities (Bmax) that varied from 50 pmol g−1 in cerebellar cortex and caudate nucleus to 200 pmol g−1 in the region of highest specific binding, the medial geniculate body.
Inward rectifier produced by Xenopus oocytes injected with mRNA extracted from carp olfactory epithelium
Authors: Yoshii Kiyonori , Kurihara Kenzo 
Published: January 2005

AbstractIonic channels encoded by mRNA extracted from carp olfactory epithelium were investigated by injection into Xenopus laevis oocytes. The oocytes expressed an inward rectifier K+‐channel, as detected under two‐electrode voltage clamp conditions. The results were as follows. An inactivating inward current appeared on hyperpolarization and increased with increasing extracellular K+ concentrations. The 0 current potentials plotted as a function of log [K+]0 in the range between 2 to 20 mM K+ fell on a straight line, with a slope of 58 mV per tenfold change in K+ concentration, indicating that the current carrier is K+. Chord conductances reached saturation levels on extreme hyperpolarization. The chord conductances at the saturation levels were 35.7, 22.5, and 13.4 μSec in 20, 10, and 5 mM extracellular K+, respectively. Extracellular application of 0.1 mM Cs+ or 0.1 mM Ba2+ blocked the inward current in 2 mM K+, Whereas 1 μM TTX or 0.3 mM Cd2+ did not affect the inward current. Inactivation of the inward currents, which became clear on extreme hyperpolarization, was suppressed with decreasing extracellular Na+ concentration. The present results suggest that carp olfactory epithelium is rich in the inward rectifier and is an excellent source of mRNA for cloning cDNA coding the inward rectifier.
Microinjection of cholecystokinin into the rat ventral tegmental area potentiates dopamine‐induced hypolocomotion
Authors: Crawley Jacqueline N. 
Published: January 2005

AbstractCholecystokinin, (CCK) 1‐400 ng, significantly potentiated the hypolocomotion induced by dopamine, when simultaneously microinjected bilaterally into the ventral tegmental area (VTA) of rat brain. Within this dose range, CCK had no effect alone on ambulatory locomotion. Topographical analysis indicated that the modulatory effect of CCK was greatest in the central and caudal regions of the VTA, and absent at sites lateral, dorsal, rostral, and caudal to the VTA. Pharmacological analysis indicated that both unsulfated CCK octapeptide (100 ng) and the C‐terminal tetrapeptide of CCK (400 ng) potentiated dopamine‐induced hypolocomotion in a manner identical with sulfated CCK octapeptide (100 ng). Proglumide, an antagonist of the peripheral‐type CCK receptor, did not block the potentiating actions of CCK, at doses of proglumide up to 500 mg/kg i.p., or 100ng into the ventral tegmental area. L‐364,718, an antagonist of the peripheral‐type CCK receptor with lesser affinity for the central‐type CCK receptor, blocked the potentiating actions of CCK at relatively high doses of L‐364,718 (1‐10 mg/kg i.p.). These findings suggest that CCK acts as a facilitatory modulator of dopamine at a central‐type CCK receptor on the A10 cell bodies.
Short‐ and long‐term survival of large neurons in the excitotoxic lesioned rat caudate nucleus: A light and electron microscopic study
Authors: Roberts Rosalinda C. , Figlia Marian Di 
Published: January 2005

AbstractLarge striatal neurons are spared in caudate tissue from postmortem brain of patients with Huntington's disease (HD) and in the rat caudate lesioned with excitotoxins at short postlesion intervals. In order to determine the survival of large neurons and other effects of excitotoxicity at longer postlesion intervals the rat caudate nucleus was examined 2,7, and 30 weeks after intrastriatal injections of the excitotoxin, quinolinic acid. The caudate nucleus diminished in size progressively up to 30 weeks postlesion due to (1) shrinkage and compacting of the lesion zone and (2) reduction in area of intact caudate, apparently due to gradual loss of the remaining caudate neurons.In Nissl‐stained sections of the lesion zone where total neuronal density was less than 5% of contralateral control, large neurons were present at all postlesion intervals, forming 38‐58% of the remaining neurons. Unexpectedly, a fivefold reduction in the number of large neurons was observed between 2 and 30 weeks postlesion. Also, at 7 and 30 weeks postlesion most of the large neurons were confined to the peripheral region of the lesion. At all postlesion intervals, large neurons retained ultrastructural integrity and some synaptic inputs despite the severe disruption of the surrounding neuropil.Surrounding the lesion zone was a transition zone which exhibited a decrease in total neuronal density to 53‐74% of control. In this region the density of large neurons was not diminished, and the proportion of large neurons was elevated in comparison to that of controls at all postlesion intervals.Findings suggest that following excitotoxic lesion of the caudate nucleus there are marked differences between short‐ and long‐term postlesion intervals in the survival and distribution of large neurons. We speculate that an imbalance in the synaptic connections with other caudate neurons leads to the persistent loss of large neurons in the lesion zone at long postlesion intervals. A transition zone surrounding the lesion, where cell loss is less severe than in the lesion zone, exhibits features more characteristic of the neuropathology of HD.
Human ventral mesencephalic xenografts to the catecholamine‐depleted striata of athymic rats: Ultrastructure and immunocytochemistry
Authors: Mahalik Thomas J. , Ströumberg Ingrid , Gerhardt Greg A. , Granholm Ann‐Charlotte , Seiger Åke , Bygdeman Marc , Olson Lars , Hoffer Barry J. , Finger Thomas E. 
Published: January 2005

AbstractOn the basis of animal studies, grafts of fetal human dopaminergic cells have been suggested as a therapy for Parkinson's disease. The purpose of this study was to characterize the ultrastructure and immunocytochemistry of human ventral mesencephalic xenografts placed into the catecholamine‐depleted striata of athymic “nude” rats.Human fetal tissue was obtained from tissue fragments derived from elective abortions during the first trimester of pregnancy. Small pieces of the basal mesencephalon were grafted into the catecholamine‐depleted striata of four athymic nude rats. The rats were allowed to survive from 3 to 6 months after grafting; following fixation, the striatal tissue containing the grafts was labeled with antibodies against tyrosine hydroxylase and serotonin.Immunocytochemistry revealed tyrosine‐hydroxylase‐like‐immunoreactive (THLI) and serotoninlike‐immunoreactive (5HTLI) cell bodies within the human grafts. Both 5HTLI and THLI fibers crossed the graft‐host interface and innervated the previously lesioned striatum. Both types of fibers also entered the host cortex from the adjacent human graft.At the ultrastructural level, THLI and 5HTLI fibers and synaptic terminals were observed in the host neuropil. THLI and 5HTLI dendrites and axon terminals were also observed in the neuropil of the grafts themselves. THLI axon terminals are not normally present in the substantia nigra. The results of our study indicate that human xenografts can survive in the neuropil of the host striatum and form morphologically appropriate synapses within the host brain.
Further evidence demonstrating that N‐methyl‐D‐aspartate and kainate activate distinct ion channels
Authors: Fong Tung Ming , Davidson Norman , Lester Henry A. 
Published: January 2005

AbstractSeveral excitatory amino acid receptors encoded by rat brain mRNA were expressed in Xenopus oocytes. Experimental protocols using an open channel blocker (MK‐801) were designed to test the common receptor‐channel hypothesis in which N‐methyl‐D‐aspartate (NMDA) and kainate activate the same ion channel but induce different open channel conformations with different ionic permeabilities. The present data demonstrate that NMDA exposes previously trapped MK‐801 molecules to the transmembrane field and accelerates their dissociation from the channel at positive potentials, while kainate lacks this effect, Therefore, kainate does not activate the same ion channel as NMDA does. Furthermore, differential inhibition of the NMDA response or the kainate response by the competitive antagonists D‐2‐amino‐5‐phosphonopentanoic acid (D‐AP5) and 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) indicates that NMDA and kainate do not share the same binding site. Thus, these several lines of evidence demonstrate that two distinct receptor‐channels are activated by NMDA and kainate, respectively.
cAMP increases the rate of GABAA receptor desensitization in chick cortical neurons
Authors: Tehrani Mohammad H. Jalilian , Hablitz John J. , Barnes Eugene M. 
Published: January 2005

AbstractDuring prolonged application of GABA to cultured neurons from the chick embryo cerebrum, whole‐cell voltage‐clamp recordings show a decline in GABA‐gated chloride currents due to desensitization. At a holding potential of –60 mV, desensitization can normally be described as a single exponential process with a time constant (τ) of 7–10 sec at a GABA concentration of 100 μM. After exposure to 50 μM forskolin, the peak amplitude of the GABA‐induced currents declined and a fast component of desensitization (τ = 0.92 sec) appeared, whereas the slow component was essentially unchanged. This effect of forskolin was reversible after washing. Similar, although less robust effects were produced by incubation with 8‐Br‐cAMP, but not by 1,9‐dideoxyforskolin. The desensitization process could also be measured by the GABA‐dependent uptake of 36Cl− into the cultured neurons. A 20‐sec incubation with 10 μM GABA in physiological saline produced a 29% inhibition of subsequent GABA‐gated 36Cl− uptake in the presence of 40 mM K+. This inhibition was increased to 64% by the addition of 100 μM forskolin to the preincubation medium. This effect of forskolin was prevented by 100 μM 2′,5′‐dideoxyadenosine, an inhibitor of adenylate cyclase. A similar acceleration of desensitization was produced by 0.5 mM 8‐Br‐cAMP or by 0.5 mM isobutylmethylxanthine, but these compounds themselves failed to produce desensitization in the absence of exogenous GABA. In the presence of GABA, cAMP analogs were effective in the order 8‐(4‐chlorophenylthio)‐cAMP > 8‐Br‐cAMP > N6, 02 ‐dibutyryl‐cAMP. The results suggest that a cAMP‐dependent phosphorylation converts the GABA receptor into a more rapidly desensitizing form.
Apparent absence of serotonin1B receptors in biopsied and post‐mortem human brain
Authors: Martial Johanne , Lal Samarthjia , Dalpé Michel , Olivier Andre , De Montigny Claude , Quirion Remi 
Published: January 2005

AbstractIn order to determine if post‐mortem delays could account for the apparent absence of 5‐HT1B sites reported in human brain, 5‐HT1B binding parameters were determined in fresh and fresh‐frozen cortical biopsies and compared to results obtained in post‐mortem tissues. Binding parameters and in vitro receptor autoradiography were performed by using two different ligands which have been shown to label 5‐HT1B sites, namely [3H]5‐HT, in presence of 100 nM 8‐OH‐DPAT, and [125I]cyanopindolol, in presence of 10 μM (–)isoproterenol. No specific binding was detected with [125I] cyanopindolol in either fresh cortical biopsies or post‐mortem tissues, suggesting that the apparent absence of 5‐HT1B receptor sites reported earlier was not related to long post‐mortem delays. Some specific labelling was seen with [3H]5‐HT, in presence of 8‐OH‐DPAT. This binding, which is unlikely to be to the 5‐HT1B type, could represent labelling to the 5‐HT1D or 5‐HT1E sites (Herrick‐Davis and Titeler: J. Neurochem., 50:1624–1631, 1988; Peroutka: Trends Neurosci., 11:496–500, 1988; Titeler and Herrick‐Davis: Soc. Neurosci. Abst., 14:553, 1988; Waeber et al: Neurosci. Lett., 88:11–16, 1988).
Ontogeny of oxytocin receptors in rat forebrain: A quantitative study
Authors: Shapiro Lawrence E. , Insel Thomas R. 
Published: January 2005

AbstractThe ontogeny of oxytocin receptors in rat forebrain was studied using the selective oxytocin receptor antagonist 125I‐d(CH2)5[Try(Me)2, THR4, Tyr‐NH29]OVT ([125I]‐OTA). With in vitro receptor autoradiography, binding was noted on the first postnatal day in dorsal subiculum and thalamus. On postnatal days 5–18, intense labeling was evident in posterior cingulate cortex, dorsal subiculum, lateral septum and the CA1 subfield of hippocampus. Of these regions only the lateral septum expressed oxytocin receptors in adult brain. Competition studies on coronal sections through posterior cinguulate, septum, and dorsal subiculum at P10 demonstrated that transient binding sites in these areas were indeed oxytocin selective (OXY>AVP>V1V2). Results of saturation studies on cingulate membranes from 10‐day‐old pups agreed favorably with previous reports of the kinetics of [125I]‐OTA binding to adult oxytocin receptors (Kd = 0.1 nM in P10 cingulate cortex vs. 0.07 nM for adult ventral subiculum). In contast to these evanescent developmental sites, oxytocin receptors in the bed nucleus of the stria terminalis and the ventromedial nucleus of the hypothalamus only appeared in adulthood, presumably in response to the surge of gonadal steroids at puberty.
Role of lipid solubility in the interaction of drugs with the N‐methyl‐D‐aspartate receptor
Authors: Reynolds Ian H. , Rush Elizabeth A. 
Published: January 2005

AbstractWe have examined the hypothesis that phenothiazines and tricyclic antidepressans interact with the N‐methyl‐D‐aspartate (NMDA) receptor bu mimicking the action of Zn2+. Using [3H]MK801 binding to well‐washed rat brain membranes, we found a disparity between the concentrations of drug required to inhibit [3H]MK801 from its binding site. These data suggest that the Zn2+ site is probably not the principle site by which tricyclic drugs inhibit NMDA receptor responses. To determine whether the effects to tricyclic drugs on the dissociation of [3H]MK801 could be explained simply by membrane stabilization, we examine dthe effect of a series of alcohols. Ethanol. isopropanol. bytanol, hexanol, and heptanol all inhibited [3H]MK801 binding. However, with the exception ot heptanol, none of the molecules altered the dissociation rate. Thus, while lipid solubility may be an important factor underlying the interactions the interactions of some drugs with the NMDA receptor, it is not sufficient to explain the effects of tricyclic antidepressants and phenothiazines in this system.
Nigrostriatal lesion alters neurophysiological responses to selective and nonselective D‐1 and D‐2 dopamine agonists in rat globus pallidus
Authors: Carlson Joanne H. , Bergstrom Debra A. , Demo Susan D. , Walters Judith R. 
Published: January 2005

AbstractThe effects of the selective D‐1 dopamine agonist SKF 38893, the selective D‐2 agonist quinpirole, and the nonselective D‐1/D‐2 agonist apomorphine on spontaneous activity of globus pallidus neurons were compared in normal control rats and rats with unilateral 6‐hydroxydopamine induced lesions of the nigrostriatal pathway. In control, unlesioned rats, SKF 38393 (0.4 and 10 mg/kg, i.v.) caused no significant net change in the activity of globus pallidus neurons, although some individual cells showed significant increases of decreases in discharge rates following 10 mg/kg SKF 38393 administration. In animals with unilateral 6‐hydroxydopamine induced lesions, SKF 38393 caused greater increases and decreases in the discharge reates of a larger percentage of pallidal cells recorded on the ipsilateral side than in control, unlesioned animals. These rate changes were effectively reversed by the D‐1 antagonist SCH 23390, but not by the D‐2 antagonist YM‐09151–2. Quinpirole (0.3 mg/kg, i.v.) produced modest rate increases in control, unlesioned animals and significantly larger rate increases in nigrostriatal lesioned animals. YM‐09151–2, but not SCH 23390, effectively reversed quinpirole's effects in the lesioned animals. As previously reported, the nonselective D‐1/D‐2 agonist apomorphine (0.3 mg/kg, i.v.) produced large increases in discharge rates of pallidal cells in control, unlesioned rats. In contrast, in nigrostriatal lesioned rats, the discharge rates of some ipsilateral pallidal neurons were markedly increased, others were decreased, and some were unaffected following apomorphine administration. The dopamine antagonist spiroperidol partially to fully reversed these rate changes. In summary, apomorphine's neurophysiological profile appears to be an exaggeration of the D‐1 agonist profile in the globus pallidus of these lesioned animals. The degree of change observed after apomorphine administration is consistent with results from other studies that have indicated that a synergistic interaction between effects triggered by stimulation of the two receptor subtypes can occur in these animals, as in control, unlesioned animals. However, these results further show that in rats with unilateral nigrostriatal lesions, the denervated dopamine receptors or the processes they mediate are altered so that they no longer have the requirement seen in controls for concurrent stimulation of the complementary dopamine receptor subtype for expression of the selective agonist effects.