bluuebunny/crossref_metadata_2025_split huggingface dataset:
CCKB receptors mediate CCK‐8S‐induced activation of dorsal hippocampus CA3 pyramidal neurons: An in vivo electrophysiological study in the rat
Authors: Gronier Benjamin , Debonnel Guy 
Published: December 2004

AbstractThe sulphated octapeptide C‐terminal fragment of cholecystokinin (CCK‐8s) is present in high concentration in the mammalian brain, where it acts via two types of receptor denoted CCKA, and CCKB. In the dorsal hippocampus, CCK‐8S exerts a potent excitatory effect on pyramidal neurons. The present electrophysiological study was undertaken to determine which CCK receptor type mediates this neuronal activation. Using in vivo extracellular unitary recordings of CA3 pyramidal hippocampal neurons, we compared the effect of SNF‐8702, a potent selective CCKB receptor agonist, to that of CCK‐BS, and assessed the effects of selective CCKA, and CCKB, antagonists. CCK‐8S and SNF‐8702, microiontophoretically applied on the same neurons produced a similar degree and pattern of activation. Both CCK‐8s‐ and SNF‐8702‐induced activations were suppressed by the microiontophoretic application of the CCKB antagonist CI‐988, but not by that of the CCKA, antagonist SR 27897. CCK‐8s‐induced activation was not significantly modified by the intravenous administration of the CCK, antagonists devazepide and SR 27897. However, it was reduced by the CCKB antagonist PD 135158, administered intravenously or intracerebroventricularly, and by the intravenous administration of the CCK, antagonist L‐365,260. The intravenous administration of PD 135158 also reduced SNF‐8702‐induced activations. These results indicate that CCKB, receptors mediate CC K‐8S‐induced activation of rat CA3 pyramidal neurons. © 1995 Wiley‐Liss, Inc.
Superoxide radicals mediate the biochemical effects of methylenedioxymethamphetamine (MDMA): Evidence from using CuZn‐superoxide dismutase transgenic mice
Authors: Cadet Jean Lud , Ladenheim Bruce , Hirata Hiroshi , Rothman Richard B. , Ali Syed , Carlson Elaine , Epstein Charles , Moran Timothy H. 
Published: December 2004

AbstractThe subacute and long‐term biochemical effects of methylenedioxymeth‐amphetamine (MDMA) were assessed in homozygous and heterozygous transgenic (Tg) mice that carry the complete sequence of the human copper‐zinc (CuZn) superoxide dismutase (SOD) gene. Non‐transgenic (Non‐Tg) mice showed significant decreased in striatal dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) levels both at 24 h and at 2 weeks after a single injection of MDMA (50 mg/kg). Heterozygous SOD‐Tg mice showed DA depletion only at the 24 h time point. In contrast, homozygous SOD‐Tg mice show no DA or DOPAC depletion at either the 24 h or at the 2 week time points. Moreover, three injections of MDMA (50 mg/kg) given 24 h apart also caused marked reduction of striatal DA and DOPAC in Non‐Tg mice when these substances were measured 2 weeks after the last MDMA injection. That injection schedule also caused small decreases in DA levels in the heterozygous animals but no changes in the homozygous mice; DOPAC levels were not affected in the heterozygous nor in the homozygous SOD‐Tg mice. Furthermore, the multiple injection schedule caused significant decreases in DA and DOPAC in female Non‐Tg mice but not in the two strains of transgenic mice. Neither the single dose nor the multiple dose schedule of MDMA injections affected striatal serotonin (5‐HT) and 5‐hydroxyindoleacetic acid (5‐HIM)levels in any of the three strains of mice. These results support previous observations that MDMA‐induced biochemical effects are observed in the DA systems of mice, whereas these effects are seen in the 5‐HT systems of rats. The present observations also document for the first time a role for the production of superoxide radicals in these effects of MDMA. These mice are an important tool for dissecting pathways involved in drug‐induced neurotoxicity. © 1995 Wiley‐Liss, Inc.1This article is a US Government work and, as such, is in the public domain in the United States of America.
Spare receptors and intrinsic activity: Studies with D1 dopamine receptor agonists
Authors: Watts Val J. , Lawler Cindy P. , Gonzales Andrea J. , Zhou Qun‐Yong , Civelli Olmer , Nichols David E. , Mailman Richard B. 
Published: December 2004

AbstractThe intrinsic activities of selected dopamine D1 receptor agonists were compared in three distinct molecular expression systems, C‐6, Ltk, and GH4, cells transfected with primate D1A receptors. The influence of the cell expression system on intrinsic activity varied markedly among agonists. Dihydrexidine (DHX), a potent full agonist with dramatic antiparkinsonian actions, displayed intrinsic activity similar to dopamine in all three cell lines. In contrast, SKF82958 and SKF38393 (full and partial agonists, respectively, in rat striatum) had intrinsic activities equal to dopamine in GH4, cells that expressed a high density of D1 receptors, yet were of lower intrinsic activity in C‐6 cells having 15‐fold fewer receptors. The idea that spare receptors are one important determinant of observed intrinsic activity was explored directly by “receptor titration”, in which ca. 90% of D1 receptors in Ltk cells were inactivated using EEDQ, an irreversible antagonist. Whereas EEDQ pretreatment decreased the potency of all agonists, it changed the intrinsic activity of some, but not all, drugs. A 40% decrease was seen with the partial agonist SKF38393, and, surprisingly, a 30% decrease was seen with the purported full agonist SKF82958. Conversely, the intrinsic activity of DHX and A68930 were unaffected by the EEDQ treatment. The data demonstrate that significant and biologically meaningful differences in intrinsic efficacy (e.g., DHX vs. SKF82958) may be obscured in test systems that have sufficient receptor reserve (e.g., the striatum). Such differences in intrinsic efficacy may be an important predictor of the clinical utility of D1 agonists. © 1995 Wiley‐Liss, Inc.
From ion currents to genomic analysis: Recent advances in GABAA receptor research
Authors: Rabow Lois E. , Russek Shelley J. , Farb David H. 
Published: December 2004

AbstractThe γ‐aminobutyric acid type A (GABAA) receptor represents an elementary switching mechanism integral to the functioning of the central nervous system and a locus for the action of many mood‐and emotion‐altering agents such as benzodiazepines, barbiturates, steroids, and alcohol. Anxiety, sleep disorders, and convulsive disorders have been effectively treated with therapeutic agents that enhance the action of GABA at the GABAA receptor or increase the concentration of GABA in nervous tissue. The GABAA receptor is a multimeric membrane‐spanning ligand‐gated ion channel that admits chloride upon binding of the neurotransmitter GABA and is modulated by many endogenous and therapeutically important agents. Since GABA is the major inhibitory neurotransmitter in the CNS, modulation of its response has profound implications for brain functioning. The GABAA receptor is virtually the only site of action for the centrally acting benzodiazepines, the most widely prescribed of the anti‐anxiety medications. Increasing evidence points to an important role for GABA in epilepsy and various neuropsychiatric disorders. Recent advances in molecular biology and complementary information derived from pharmacology, biochemistry, electrophysiology, anatomy and cell biology, and behavior have led to a phenomenal growth in our understanding of the structure, function, regulation, and evolution of the GABAA receptor. Benzodiazepines, barbiturates, steroids, polyvalent cations, and ethanol act as positive or negative modulators of receptor function. The description of a receptor gene superfamily comprising the subunits of the GABAA, nicotinic acetylcholine, and glycine receptors has led to a new way of thinking about gene expression and receptor assembly in the nervous system. Seventeen genetically distinct subunit subtypes (αl‐α6, βl‐β4, γl‐γ4,δ, pl‐p2) and alternatively spliced variants contribute to the molecular architecture of the GABAA receptor. Mysteriously, certain preferred combinations of subunits, most notably the αlβ2γ2 arrangement, are widely codistributed, while the expression of other subunits, such as βl or α6, is severely restricted to specific neurons in the hippocampal formation or cerebellar cortex. Nervous tissue has the capacity to exert control over receptor number, allosteric uncoupling, subunit mRNA levels, and posttranslational modifications.
Sensitivity of rat frontal cortical neurones to nicotine is increased by chronic administration of nicotine and by lesions of the nucleus basalis magnocellularis: Comparison with numbers of [3H]nicotine binding sites
Authors: Abdulla Fuad A. , Calaminici Mariarita , Wonnacott Sue , Gray Jeffrey A. , Stephenson John D. , Sinden John D. 
Published: December 2004

AbstractThe effects of chronic nicotine treatment and of unilateral AMPA lesion of the nucleus basalis magnocellularis (nbm) on the sensitivity of frontal cortical neurones to iontophoretically applied nicotine were studied. Chronic nicotine treatment increased the number of L3H1nicotine binding sites from 2.9 to 3.9 pmolg−1 wet weight, and increased the proportion of cortical neurones responding to nicotine from 32.3% to 60.0%. After unilateral nbm lesions, the densities of AChE‐positive fibers and [3H]nicotine binding sites were reduced by approximately 97% and 55%, respectively, and the proportion of neurones responding to nicotine increased from 32.3% to 53.8%. The two treatments, chronic nicotine administration and nbm lesion, also increased the size of individual neuronal responses, prolonged their duration, and shortened the response latency. Responses to glutamate were unaffected by either procedures. The results show that the increase in [3H]nicotine binding produced by chronic nicotine administration is associated with an increased response to iontophoretically applied nicotine, suggesting that the receptor upregulation induced by the chronic treatment were functional. Less easily explained is the association between increased sensitivity of frontal cortical neurons to nicotine after nbm lesion with a decreased receptor density. It is suggested that a substantial proportion of nicotinic receptors are located presynaptically, and that their loss after lesion concealed an upregulation at postsynaptic sites. © 1995 Wiley‐Liss, Inc.
Biochemical actions of chronic ethanol exposure in the mesolimbic dopamine system
Authors: Ortiz Jordi , Fitzgerald Lawrence W. , Charlton Maura , Lane Sarah , Trevisan Louis , Guitart Xavier , Shoemaker William , Duman Ronald S. , Nestler Eric J. 
Published: December 2004

AbstractIn previous studies, we have demonstrated that chronic administration of morphine or cocaine produces some common biochemical adaptations in the ventral tegmental area (VTA) and nucleus accumbens (NAc), components of the mesolimbic dopamine system implicated in the reinforcing actions of these and other drugs of abuse. Since this neural pathway is also implicated in the reinforcing actions of ethanol, it was of interest to determine whether chronic ethanol exposure results in similar biochemical adaptations. Indeed, as seen for chronic morphine and cocaine treatments, we show here that chronic ethanol treatment increased levels of tyrosine hydroxylase and glial fibrillary acidic protein immunoreactivity, and decreases levels of neurofilament protein immunoreactivity, in the VTA. Also like morphine and cocaine, ethanol increases levels of cyclic AMP‐dependent protein kinase activity in the NAc. These actions of ethanol required long‐term exposure to the drug, and were in most cases not seen in the substantia nigra or caudate‐putamen, components of the nigrostriatal dopamine system studied for comparison.Altered levels of tyrosine hydroxylase in catecholaminergic cells frequently reflect altered states of activation of the cells. Moreover, increasing evidence indicates that ethanol produces many of its acute effects on the brain by regulating NMDA glutamate and GABA receptors. We therefore examined the influence of chronic ethanol treatment on levels of expression of specific glutamate and GABA receptor subunits in the VTA. It was found that long‐term, but not short‐term, ethanol exposure increased levels of immunoreactivity of the NMDARl subunit, an obligatory component of NMDA glutamate receptors, and of the Glu Rl subunit, a component of many AMPA glutamate receptors; but at the same time, long‐term ethanol exposure decreased immunoreactivity levels of the α1 subunit of the GABAA receptor complex. These changes are consistent with an increased state of activation of VTA neurons inferred from the observed increase intyrosine hydroxylase (TH) expression.These results demonstrate that chronic ethanol exposure results in several biochemical adaptations in the mesolimbic dopamine system, which may underlie prominent changes in the structural and functional properties of this neural pathway related to alcohol abuse and alcoholism. © 1995 Wiley‐Liss, Inc.
Interhemispheric modulation of dopamine receptor interactions in unilateral 6‐OHDA rodent model
Authors: Lawler Cindy P. , Gilmore John H. , Watts Val J. , Walker Q. David , Southerland Stan B. , Cook Larry L. , Mathis Chet A. , Mailman Richard B. 
Published: December 2004

AbstractA critical assumption in the unilateral 6‐hydroxydopamine (6‐OHDA) model is that interactions between the intact and denervated hemispheres do not influence the response to insult. The present study examined this issue by assessing the effects of unilateral substantia nigra 6‐OHDA lesions in rats that previously had received corpus callosum transections, a treatment designed to minimize interhemispheric influences. Quantitative autoradiography in the caudate‐putamen ipsilateral to the lesion revealed that corpus callosum transection did not alter the increase in D2‐like receptors ([125I]‐epidepride‐labeled sites) that is induced by unilateral 6‐OHDA lesion. There were no effects of either 6‐OHDA lesion or transection on D1 receptor density ([l25I]‐SCH23982 autoradiography). As a functional endpoint, dopamine‐stimulated cAMP efflux was measured in superfused striatal slices. In this paradigm, the net effect of dopamine (DA) represents a combination of D1 receptor‐mediated stimulation and D2 receptor‐mediated inhibition. 6‐OHDA lesion increased cAMP efflux induced by exposure to 100 p.M DA alone; corpus callosum transection did not alter this effect. An interaction between 6‐OHDA lesion and transection status was revealed, however, by comparison of results obtained with DA alone vs. DA plus the D2 antagonist sulpiride (to block the D2 inhibitory effects of 100 p.M DA). This comparison revealed two important effects of 6‐OHDA lesion in rats with an intact corpus callosum: (1)a moderate decrease in dopamine Dl receptor‐mediated stimulation; and (2) a dramatic decrease in the ability of D2 receptors to inhibit this stimulation. Corpus callosum transection prevented these effects of 6‐OHDA. These results provide a biochemical demonstration of D1:D2 receptor uncoupling in unilateral 6‐OHDA lesioned rats, and suggest that interhemispheric influences (e.g., contralateral cortico‐striatal glutamatergic projections) may contribute to lesion‐induced alterations in D1:D2 receptor interactions. © 1995 Wiley‐Liss, Inc.
Effects of coexisting neurochemicals on the release of serotonin from the intermediate area of rat thoracic spinal cord
Authors: Yang Ling , Helke Cinda J. 
Published: December 2004

AbstractSerotonin (5‐HT), substance P (SP), neurokinin A (NKA), and thyrotropin‐releasing hormone (TRH) coexist in the nerve terminals of the intermediolateral cell column (IML) of the thoracic spinal cord. The Ca2+‐dependent release of 5‐HT from the microdissected intermediate area (including the IML) of the rat thoracic spinal cord, and the 5‐HT1B autoreceptor regulator of 5‐HT release, were previously demonstrated. In this paper, the effects of SP, NKA, TRH, and/or their analogs on the release of [3H]5‐HT from the intermediate area were investigated using an in vitro superfusion system. Both SP (the endogenous ligand for neurokinin‐1 (NK1) receptor) and an NK1, agonist (GR 73632) significantly increased the basal release of [33H]5‐HT. SP and GR 73632 did not change the K+‐stimulated release of [3H]5‐HT. The effect of the NK1 agonist on the basal release of [3H]5‐HT was dose‐dependent, was reduced by an NK1 antagonist (GR 82334), and was not dependent on extracellular Ca2+. Neither NKA, an NK2, agonist (GR 64349), nor a TRH analog (MK‐771) altered the basal or stimulated release of [3H]5‐HT. These data suggest that basal release of 5‐HT from the intermediate area of the rat thoracic spinal cord is regulated by SP (acting through an NK1 receptor), but not by NKA or TRH. These results provide evidence for the role of SP as a modulator of serotoninergic neurons in the intermediate area of the thoracic spinal cord, and may help to clarify the role of coexisting neurochemicals in the spinal regulation of the sympathetic nervous system. © 1995 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.
N‐methyl‐D‐aspartate acutely increases proenkephalin mRNA in the rat striatum
Authors: Beckstead R. M. 
Published: December 2004

AbstractStudies in which glutamate (GLU) neurotransmission has been reduced at striatal synapses have shown that GLU influences the biosynthesis of certain peptide cotransmitters by striatal neurons. The present experiment was designed to test the effects of direct activation of the NMDA or AMPA types of GLU receptor on the levels of two mRNAs that encode the peptide cotransmitters met5‐enkephalin (ME) and sub‐ stance P (SP). In situ hybridization histochemistry of forebrain tissue sections from rats 8 h after a single intracerebroventricular infusion of NMDA or AMPA revealed a significant and dose‐dependent elevation (to a maximum of almost 50%) of striatal ME mRNA when compared to vehicle‐injected controls. SP mRNA was not significantly affected. NMDA was more effective than AMPA over the dose range used. Pretreatment with a potent and highly specific AMPA antagonist (NBQX) predictably blocked the AMPA‐mediated elevation, and was only slightly effective against the NMDA‐induced response. In striking contrast, pretreatment with a potent and highly selective NMDA antagonist (CGP37849) fully opposed both the NMDA‐ and the AMPA‐mediated elevation of ME mRNA. These data further implicate the NMDA receptor in the regulation of peptide cotransmitter gene transcription. They suggest also that the AMPA receptor may play an indirect, synergistic role in the genetic responses of striatal neurons to GLU transmission. © 1995 Wiley‐Liss, Inc.
Mapping dopamine transporters in the human brain with novel selective cocaine analog [125I]RTI‐121
Authors: Staley J. K. , Boja J. W. , Carroll F. I. , Seltzman H. H. , Wyrick C. D. , Lewin A. H. , Abraham P. , Mash D. C. 
Published: December 2004

AbstractThe novel cocaine analog RTI‐121[3β‐(4‐iodophenyl)tropane‐2β‐carboxylic acid isopropyl ester] was evaluated as a probe for the in vitro labeling and localization of the dopamine transporter in the human brain. Saturation binding experiments conducted in sucrose‐phosphate buffer (10 mM sodium phosphate, pH 7.4, 0.32 M sucrose) revealed high‐ and low‐affinity binding components with affinity values (KD) of 0.25 ± 0.04 and 4.9 ± 1.6 nM (mean ± SE) and densities (Bmax) of 56.8 ± 13.8 and 147.7 ± 23.4 pmol/g tissue, respectively. In contrast, when saturation binding experiments were performed in phosphate‐buffered saline (10 mM Na2HP04, 1.8 mM KH2Po4, 136 mM NaCl,2.8 mM KC1, 10 mM NaI, pH 7.4), a 9‐fold decrease in the density of the low‐affinity component was noted, suggesting that the low‐affinity RTI‐121 binding site is associated with the region of the transporter involved in the ionic dependence of substrate recognition andor uptake. The rank order. of potency for inhibition of [1251]RTI‐121 binding to human caudate membranes demonstrates that the radioligand selectively labels the dopamine transporter (GBR 12909 > RTI‐121 > mazindol > nomifensine > (−)cocaine > desipramine > citalopram). Autoradiograpliic mapping of [1251]RTI‐121 revealed very high densities of cocaine recognition sites over areas known to be rich in dopaminergic innervation, including the caudate, putamen, and nucleus accumbens. Moderate densities were also observed over the substantia nigra and the ventral tegmental area. Low‐to‐background labeling of [1251]RTI‐ 121 was seen throughout the cerebral cortex, amygdaloid nuclei, globus pallidus, and thalamus. In comparison with the autoradiographic distribution of the cocaine analogs L3H1WIN 35,428 (or CFT) and [1251]RTI‐55 (or β‐CIT), the labeling pattern for [1251]RTI‐121 was more restricted. These studies demonstrate that [1251]RTI‐121 labels dopamine‐rich brain regions with greater selectivity than other currently available cocaine analogs, which makes it a potentially superior imaging probe for mapping the dopamine transporter in the human brain. © 1995 WiIey‐Liss, Inc.
Prenatal diagnosis of severe structural congenital malformations in Europe
Authors: Garne E. , Loane M. , Dolk H. , De Vigan C. , Scarano G. , Tucker D. , Stoll C. , Gener B. , Pierini A. , Nelen V. , Rösch C. , Gillerot Y. , Feijoo M. , Tincheva R. , Queisser‐Luft A. , Addor M.‐C. , Mosquera C. , Gatt M. , Barisic I. 
Published: December 2004

AbstractObjectivesTo assess at a population‐based level the frequency with which severe structural congenital malformations are detected prenatally in Europe and the gestational age at detection, and to describe regional variation in these indicators.MethodsIn the period 1995–1999, data were obtained from 17 European population‐based registries of congenital malformations (EUROCAT). Included were all live births, fetal deaths and terminations of pregnancy diagnosed with one or more of the following malformations: anencephalus, encephalocele, spina bifida, hydrocephalus, transposition of great arteries, hypoplastic left heart, limb reduction defect, bilateral renal agenesis, diaphragmatic hernia, omphalocele and gastroschisis.ResultsThe 17 registries reported 4366 cases diagnosed with the 11 severe structural malformations and of these 2300 were live births (53%), 181 were fetal deaths (4%) and 1863 were terminations of pregnancy (43%); in 22 cases pregnancy outcome was unknown. The overall prenatal detection rate was 64% (range, 25–88% across regions). The proportion of terminations of pregnancy varied between regions from 15% to 59% of all cases. Gestational age at discovery for prenatally diagnosed cases was less than 24 weeks for 68% (range, 36–88%) of cases. There was a significant relationship between high prenatal detection rate and early diagnosis (P < 0.0001). For individual malformations, the prenatal detection rate was highest for anencephalus (469/498, 94%) and lowest for transposition of the great arteries (89/324, 27%). Termination of pregnancy was performed in more than half of the prenatally diagnosed cases, except for those with transposition of the great arteries, diaphragmatic hernia and gastroschisis, in which 30–40% of the pregnancies with a prenatal diagnosis were terminated.ConclusionEuropean countries currently vary widely in the provision and uptake of prenatal screening and its quality, as well as the ‘culture’ in terms of decision to continue the pregnancy. This inevitably contributes to variation between countries in perinatal and infant mortality and in childhood prevalence and cost to health services of congenital anomalies. Copyright © 2004 ISUOG. Published by John Wiley & Sons, Ltd.