bluuebunny/crossref_metadata_2025_split huggingface dataset:
[3H]1‐[2‐(2‐thienyl)cyclohexyl]piperidine labels two high‐affinity binding sites in human cortex: Further evidence for phencyclidine binding sites associated with the biogenic amine reuptake complex
Authors: Akunne Hyacinth C. , Reid Audrey A. , Thurkauf Andrew , Jacobson Arthur E. , de Costa Brain , Rice Kenner C. , Heyes Melvyn P. , Rothman Richard B. 
Published: December 2004

AbstractPrevious work demonstrated two high‐affinity PCP binding sites in guinea pig brain labeled by [3H]TCP (1‐{1‐[2‐thienyl]cyclohexyl}piperidine): site 1 {N‐methyl‐D‐aspartate [NMDA]‐associated} and site 2 {dopamine‐reuptake complex associated}. The present study examined brain membranes prepared from various species, including human, for the presence of site 2, defined as binding in the presence of (+)‐5‐methyl‐10, 11‐dihydro‐5H‐dibenzo[a,d]cyclohepten‐5, 10‐imine maleate ((+)‐MK801) minus binding in the presence of 10 μM TCP (nonspecific binding). Studies were conducted in absence of sodium which was found to be inhibitory to [3H]TCP binding. The results demonstrated detectable levels of site 2 in brain membranes of guinea pig, rabbit, pig, mouse, sheep, and human but not in the rat or chicken. Using human cortical membranes, site 2 was the predominant binding site. Detailed studies conducted with human cortical tissue showed that high‐affinity dopamine {1‐[2‐]bis(4[fluorophenyl)[methoxy]ethyl]4‐(3‐phenylpropyl)piperazine (GBR12909)}, [1, 2]benzo(b)thiophenylcyclo‐hexylpiperidine (BTCP), and serotonin (fluoxetine) uptake inhibitors produced a wash‐resistant inhibition of [3H]TCP binding to site 2, but not site 1. Preincubation of guinea pig brain membranes with BTCP was shown to produce an increase in the dissociation rate of [3H]TCP from PCP site 2. Structure activity studies with various uptake inhibitors showed that GBR12909, benztropine, fluoxetine, and BTCP have higher affinity for site 2 than for site 1. (+)‐MK801, ketamine, and tiletamine were very selective for site 1, whereas dexoxadrol and TCP were moderately selective for site 1. These results suggest that human cortex possesses high‐affinity PCP binding sites associated with biogenic reuptake binding sites, and that guinea pig brain, but not rat brain, may be an appropriate animal model for studying PCP site 2 in human brain.
Dopamine depletion produces augmented behavioral responses to a Mu‐, but not a delta‐opioid receptor agonist in the nucleus accumbens: Lack of a role for receptor upregulation
Authors: Churchill Lynn , Kalivas Peter W. 
Published: December 2004

AbstractMicroinjection of either m̈ ‐ or ð‐ opioid agonists into the nucleus accumbens produces an increased locomotor activity, and when the dopaminergic innervation of the nucleus accumbens is bilaterally lesioned, the locomotor response to the microinjection of mixed m̈‐ and ð‐opioid is augmented. To determine whether the lesion‐induced augmentation to opioids is specific to m̈‐ or ð‐ opioid receptor activation, dopamine innervation of the nucleus accumbens was lesioned with 6‐hydroxydopamine (6‐OHDA), and the motor stimulant response to intra‐accumbens microinjection of the selective m̈‐ opioid agonist, Tyr‐D‐Ala‐Gly‐mePhe‐Gly‐OH (DAMGO), was compared to that of the ð‐opioid agonist, [D‐penicillamine2.5]‐enkephalin (DPDPE). The lesions caused a 95% depletion of tissue dopamine levels in the nucleus accumbens of the DAMGO‐injected rats compared to sham‐lesioned rats. Horizontal and vertical photocell counts were significantly increased in response to DAMGO in 6‐OHDA‐lesioned compared to the sham‐lesioned rats. This behavioral augmentation was dose dependent and blocked by naloxone. In rats with similar accumbal dopamine depletions (94%), the locomotor response to DPDPE was not enhanced. The augmentation in the behavioral response to DAMGO was not associated with a change in the Bmax or Kd of [125I] DAMGO binding in nucleus accumbens homogenates form lesioned rats. Likewise, using quantitative receptor autoradiography, no difference between 6‐OHDA‐ and sham‐lesioned rats was observed in [125I]DAMGO or [125I]DPDPE binding. Therefore, the augmented behavioral response to opioids in the nucleus accumbens following dopamine depletion relies predominately on ð‐opioid receptor stimulation. However, this augmentation is not mediated by an alteration in the number or affinity of these receptors. © Wiley‐Liss, Inc.
Possible functions of a new genetic marker in central nervous system: The sulfated glycoprotein‐2 (SGP‐2)
Authors: Michel Denis , Chabot Jean‐Guy , Moyse Emmanuel , Danik Marc , Quirion Rémi 
Published: December 2004

AbstractThis brief review discusses the recent characterization in the brain of a gene coding for a protein that may be involved in programmed cell death and/or brain plasticity. We will term it sulfated glycoprotein‐2 (SGP‐2), the name corresponding to the first cDNA characterized. Recent studies have demonstrated the overexpression of this sulfated glycoprotein in various CNS disorders, such as certain gliomas, Alzheimer's disease and epilepsy, as well as after experimental brain injury in animals where different cell types were undergoing tissue remodelling or cell death. In peripheral tissues, SGP‐2 gene expression has been found to be strikingly increased following experimental manipulations in which cells of injured tissues were undergoing programmed cell death or apoptosis. The results reported thus far are intriguing and suggest the possible involvement of SGP‐2 in apoptotic mechanisms as well as its interaction with components of the immune system possibly associated with cell death in neurodegenerative disorders. © 1992 Wiley‐Liss, Inc.
Adenosine‐mediated synaptic inhibition: Partial blockade by barium does not prevent anti‐epileptiform activity
Authors: Birnstiel Susanne , Gerber Urs , Greene Robert W. 
Published: December 2004

AbstractAdenosine‐induced inhibition of evoked postsynaptic potentials (PSPs) and epileptiform burst firing in the CA1 subfield of rat hippocampal slices was studied with intracellular recordings in vitro. Adenosine (50 μM) caused a membrane hyperpolarization which was abolished during superfusion with 2 mM Ba2+. The adenosine‐induced inhibition of the PSPs was still evident, although the magnitude of the effect was significanty reduced. Adenosine also reduced Ba2+‐induced burst firing, but less effectively than it did bursts evoked by TEA (5 mM). The results suggest that adenosine inhibits synaptic transmission and epileptiform activity by at least 2 mechanisms: a postsynaptic barium‐sensitive increase in gK and a presynaptic effect independent of this adenosine‐evoked outward potassium conductance. © Wiley‐Liss, Inc.
In vivo binding of [125I] RTI‐55 to dopamine transporters: Pharmacology and regional distribution with autoradiography
Authors: Cline Elizabeth J. , Scheffel Ursula , Boja John W. , Mitchell W. Mark , Carroll F. Ivy , Abraham P. , Lewin Anita H. , Kuhar Michael J. 
Published: December 2004

AbstractPrevious studies have demonstrated that para‐substituted WIN 35,065‐2 analogs of cocaine show high binding affinity for dopamine uptake sites both in vitro and in vivo, and inhibit DA uptake in vitro. These analogs also produce potent cocaine‐like behavioral effects in various procedures. The purpose of the present studies was to evaluate the iodinated WIN 35,065‐2 analog [125I] RTI‐55 as an in vivo ligand for the DA transporter. Following intravenous injection in mice, [125I] RTI‐55 showed highest accumulation in areas with high densities of dopamine uptake sites. Light microscopic autoradiography was used to examine binding with higher resolution. Displacement studies demonstrated that [125I] RTI‐55 binding in dopamine containing regions, striatum and olfactory tubercles, was saturable and inhibited by other cocaine analogs. GBR 12909 and WIN 35,428 significantly inhibited [125I] RTI‐55 binding in striatum, while paroxetine significantly inhibited hypothalamic binding but had little effect in striatum. The latter finding suggests that [125I] RTI‐55 also binds to the serotonin transporter. Haloperidol had no effect on [125I] RTI‐55 binding in any brain region measured. In addition, treatment of animals with the dopamine neurotoxin MPTP caused significant reductions in striatal [125I] RTI‐55 binding. The results of these studies indicate that [125I] RTI‐55 binds primarily to the dopamine transporter in the mouse striatum in vivo. Published 1992 Wiley‐Liss, Inc.
Biosynthesis of dopamine and serotonin in the rat brain after repeated cocaine injections: A microdissection mapping study
Authors: Baumann Michael H. , Raley Thomas J. , Partilla John S. , Rothman Richard B. 
Published: December 2004

AbstractThe purpose of the present study was to examine the effects of chronic cocaine on dopamine (DA) and serotonin (5‐HT) synthesis in several rat brain regions implicated in drug reinforcement. Male rats were treated twice daily with cocaine (15 mg/kg, ip) or saline for 1 week. After 42 hr of abstinence, rats were challenged with either cocaine (15 mg/kg, ip) or saline, followed by the aromatic L‐amino acid decarboxylase inhibitor 3‐hydroxybenzylhydrazine (NSD‐1015; 100 mg/kg, ip). Animals were decapitated 30 min after NSD‐1015 and discrete brain regions were microdissected from 300 μm frozen sections. Postmortem tissue levels of 3, 4‐dihydroxyphenylalanine (DOPA) and 5‐hyroxytryptophan (5‐HTP) were quantified by HPLC with electrochemical detection and used to estimate biosynthesis of DA and 5‐HT, respectively. In chronic saline‐treated rats, cocaine dramatically suppressed DA and 5‐HT synthesis in all forebrain regions examined, including: medial prefrontal cortex, nucleus accumbens, caudate nucleus, olfactory tubercle, and basolateral amygdala. The degree of inhibition ranged from 35‐65% and was more pronounced in 5‐HT neurons compared to DA neurons in the same tissue sample. In general, chronic cocaine did not significantly alter basal levels of DOPA or 5‐HTP; a notable exception was lateral hypothalamus, where chronic cocaine reduced basal DA synthesis to 75% of control. After repeated cocaine injections, the synthesisiinhibiting effect of a challenge injection of cocaine was attenuated in many brain areas. These data suggest that whereas acute cocaine decreases DA and 5‐HT synthesis in forebrain, chronic cocaine is not neurotoxic to DA and 5‐HT neurons. In addition, the mechanism(s) mediating cocaine‐induced suppression of monoamine synthesis may become desensitized by chronic exposure to the drug. Published 1993 Wiley‐Liss, Inc.
Hippocampal CRF, NE, and NMDA system interactions in memory processing in the rat
Authors: Lee E. H. Y. , Lee C. P. , Wang H. I. , Lin W. R. 
Published: December 2004

AbstractIn the present study, we investigated the neural mechanisms of corticotropin‐releasing factor (CRF) and the interactions among CRF, norepinephrine (NE), and N‐methyl‐D‐aspartate (NMDA) systems in the dentate gyrus (DG) of hippocampus in modulating the memory process of rats. One‐way passive avoidance task was adopted. Results indicated that CRF (80 ng), when directly injected into the DG, consistently and significantly enhanced memory retention in rats. The noradrenergic neurotoxin DSP‐4, at a high dose (4 μg), impaired memory. DSP‐4 at a moderate dose (2 μg), which did not affect retention alone, antagonized the memory‐enhancing effect of CRF. Similarly, the ß‐adrenergic antagonist propranolol, at a high dose (8 μg), reduced retention. At a low dose (80 ng), which did not markedly affect retention by itself, propranolol also prevented the memory‐improving effect of CRF. Moreover, direct NE infusions to the DG significantly improved retention performance in a dose‐sensitive manner. Coadministration of CRF and NE did not further enhance retention. These results together suggest that CRF and NE facilitated memory probably through the same instead of independent mechanisms. In contrast, the selective NMDA receptor antagonists 2‐amino‐5‐phosphonopentanoate (AP5) and MK801, at high doses markedly impaired memory retention (0. 8 and 3. 2 μg for AP5, 2 and 10 μg for MK801). At a dose of MK801 that did not significantly alter retention alone (80 ng), it completely blocked the memory‐facilitating effect of CRF. These results indicate that CRF enhanced memory indirectly through NMDA receptor mediation also. Finally, MK801 at 80 ng also successfully antagonized the memory‐facilitating effect of NE in the DG. We have demonstrated that MK801, at the dose chosen for interaction studies, did not markedly alter locomotor activity. These results together suggest that CRF, through a presynaptic facilitation mechanism, possibly facilitates NE release in the DG: increased NE release and stimulation of ß‐adrenergic receptors in the DG result in NMDA receptor activations in the same area. This sequence of events enhance the memory consolidation process in the hippocampus and explained the neural mechanism of CRF in facilitating retention performance in rats. The same neuropeptide/neurotransmitter interactions may have other physiological and neuropathological implications. © 1993 Wiley‐Liss, Inc.
Alterations in the dopaminergic receptor system after chronic administration of cocaine
Authors: Alburges Mario E. , Narang Neelam , Wamsley James K. 
Published: December 2004

AbstractSeveral studies suggest that one of the most important factors contributing to cocaine dependence is an alteration in the actions of the neurotransmitter dopamine in the central nervous system. In order to understand some of the neuroreceptor consequences of cocaine administration, groups of rats were injected with cocaine (2 daily doses of 15 mg/kg) for 1 to 21 days. Binding of [3H]cocaine, [3H]SCH23390, [3H]raclopride, and [3H]BTCP in striatal and cortical tissue from the treated animals was compared to controls. [3H]Cocaine binding was increased by the drug in the striatum and cortex at days 14 and 21, respectively. The binding of [3H]SCH23390 to D1 dopamine receptors was significantly increased at day 3 of cocaine exposure. In striatal membranes, [3H]BTCP binding to dopamine uptake sites was significantly increased after day 7, whereas binding in cortical membranes was increased from day 1. [3H]Raclopride binding to D2 dopamine receptors remained unchanged throughout the study in both cortical and striatal tissues.These results indicate that repeated exposure to cocaine produces an upregulation (possible supersensitivity) in cortical D1, cocaine, and DA‐uptake sites which occurs in a time‐dependent manner. These increases are coupled with an upregulation in striatal D1, cocaine, and DA‐uptake sites, without simultaneous changes in D2 receptors. Thus, cocaine's effects are not uniformly distributed across all brain regions, but rather are focused within areas of the dopamine system. © 1993 Wiley‐Liss, Inc.
Dopamine transporter mutants selectively enhance MPP+ transport
Authors: Kitayama Shigeo , Wang Jia‐Bei , Uhl George R. 
Published: December 2004

AbstractMPP+ (1‐methyl‐4‐phenylpyridinium), a dopaminergic neurotoxin that provides the best available experimental model of Parkinson's disease, is selectively concentrated in dopamine neurons by the dopamine transporter (DAT). DAT also serves as a primary recognition site for cocaine. To help define selective molecular mechanisms by which MPP+ uptake occurs, we have tested dopamine transporters mutated in several residues for their abilities to accumulate dopamine and MPP+, and to bind a cocaine analog. Mutants in DAT 7th and 11th hydrophobic putative transmembrane domains increase MPP+ uptake velocity and affinity (1/KD), respectively. These mutations exert much more modest effects on dopamine uptake and have little impact on cocaine analog binding. These findings provide the first example of mutations that enhance transport and identify specific DAT amino acids selectively involved in neurotoxin uptake. They may also have implications for the feasibility of developing drugs that could specifically block accumulation of Parkinsonism‐inducing neurotoxins. © 1993 Wiley‐Liss, Inc.
Identification and characterization of striatal cell subtypes using in vivo intracellular recording in rats. I. Basic physiology and response to corticostriatal fiber stimulation
Authors: Onn Shao‐Pii , Berger Theodore W. , Grace Anthony A. 
Published: December 2004

AbstractThe electrophysiological characteristics of two subtypes of striatal neurons, identified by their distinct patterns of response to paired impulse stimulation of corticostriatal afferents, were compared using in vivo intracellular recordings in rats. As observed in previous extracellular recording studies, the majority of neurons (73%) were found to be of the Type II class, with the remaining cells exhibiting the Type I response patern. For all cells, cortical stimulation elicited 5–30 mV EPSPs at latencies ranging from 2.0–5.3 msec; Increasing the stimulating current intensity caused a progressive increase in the amplitude of the evoked EPSPs without altering their latencies, suggesting that the EPSPs are monosynaptically mediated. Both the average amplitude and duration of the evoked EPSPs at spike threshold in Type I neurons (9.8 ± 1.7 mV, 11.8 ± 2.8 msec; mean ± SEM) were significantly smaller than those of Type II cells (20.3 ± 1.4 mV, 22.7 ± 2.1 msec). Although the average latency to the onset of the EPSP was similar for both cell classes (Type I cells: 2.3 ± 0.3 msec; Type II cells: 2.2 ± 0.2 msec), the EPSPs in Type I cells reached peak amplitude and the spikes were triggered at significantly longer latencies than in the Type II cells (peak I: 11.2 ± 2.5 msec vs. II: 7.6 ± 0.7 msec; spike I: 8.0 ± 1.2 msec vs. II: 5.7 ± 0.4 msec).Striatal neurons had a comparatively hyperpolarized resting membrane potential (−70.2 ± 2.1 mV) and had an average input resistance of 35.4 ± 7.6 MΩ. Overall, striatal neurons exhibited low levels of spontaneous activity (0.6 ± 0.7 Hz) with 50% of the neurons being quiescent. Type I cells exhibited significantly higher firing rates (3.2 ± 0.8 Hz) than Type II cells (0.8 ± 0.3 Hz), although their resting membrane potentials were not significantly different. Spontaneously occurring spikes had an average amplitude of 72.7 ± 3.4 mV and spike thresholds of −50.1 ± 1.5 mV. Irregularly occurring depolarizing plateau potentials, which typically gave rise to spike discharge, were frequently observed in both spontaneously firing and quiescent neurons. A small proportion of the cells recorded (3/55) exhibited a Type I response pattern but had unique physiological characteristics that were similar to those described by others as arising from large, aspiny striatal neurons.The present study shows that these two physiologically distinct neuron types appear to be similar in terms of their passive membrane properties (e.g., resting membrane potentials, input resistance, etc.) and firing characteristics, despite their unique patterns of response to corticostriatal stimulation. Therefore, the source of the distinct paired impulse response profiles of these neurons is more likely to arise from differences in their afferent drive than from a heterogeneity in their membrane properties. © 1994 Wiley‐Liss, Inc.
Autoradiographic distribution of Mu opioid receptors in the brains of Cu/Zn‐superoxide dismutase mice
Authors: Kujirai Kayoko , Carlson Elaine , Epstein Charles J. , Cadet Jean Lud 
Published: December 2004

AbstractSuperoxide dismutase (SOD) is an important free radical scavenging enzyme which dismutates the superoxide anion radical. We have evaluated the role of SOD in the regulation of opioid receptors by comparing the concentration of μ opioid receptors labeled with [3H]DAGO (Tyr‐D‐Ala‐Gly‐NMe‐Phe‐Gly‐ol) in SOD‐transgenic (SOD‐Tg) mice and their non‐transgenic (Non‐Tg) littermates. SOD‐Tg mice had higher maximal binding capacity (Bmax) in the shell division of the nucleus accumbens (NAcshell) in comparison to Non‐Tg littermates. There were no differences in Bmax in μ receptors in the core subdivision of the nucleus accumbens (NAc‐core). There were no significant differences in receptor affinity (Kd) in either the NAc‐shell or in the NAc‐core. Moreover, there were no significant differences in either Bmax or Kd in the matrices nor in the patches of any of the striatal subdivisions. However, in a fashion similar to the situation in the NAc‐shell, [3H]DAGO binding in the substantia nigra pars compacta (SNpc), the ventral tegmental area (VTA), and the ventral part of the central grey was significantly higher in the SOD‐Tg mice in comparison to Non‐Tg mice. The present results are discussed in terms of their support for a possible involvement of free radicals in the differences observed in various regions of the SOD‐Tg and control mice, which differ in their ability to scavenge the superoxide anion. Moreover, because of the differences in β‐opioid receptors in the NAc‐shell, these transgenic mice might provide an excellent model in which to evaluate the role of the two accumbal subdivisions in paradigms of drug addiction, which appears to depend on the functional integrity of the mesocorticolimbic system. © 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.
MPTP‐induced oxidative stress and neurotoxicity are age‐dependent: Evidence from measures of reactive oxygen species and striatal dopamine levels
Authors: Ali Syed F. , David Stanley N. , Newport Glenn D. , Cadet Jean L. , Slikker William 
Published: December 2004

Abstract1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) causes marked depletion of dopamine (DA) levels and reduction in the activity of tyrosine hydroxylase (TH) in the nigrostriatal DA pathway. In the brain, the enzyme monoamine oxidase B converts MPTP to 1‐methyl‐4‐phenylpyridinium (MPP+) which enters DA terminals via DA uptake sites. Within the DA terminals, MPP+ blocks the mitochondrial complex I and causes ATP depletion. This is thought to be the main cause of MPTP‐induced terminal degeneration. In addition, reactive oxygen species (ROS) generated after blockade of the complex I as well as those generated due to DA oxidation may participate in MPTP‐induced dopaminotoxicity. The present study sought to determine if a single injection of a large dose of MPTP generates ROS. We also sought to determine if these changes as well as changes in DA levels were correlated and age‐dependent. Toward that end, we have used C57/B6N male mice that were 22 days or 12 months old. These animals were injected with a single dose of MPTP (40 mg/kg, ip). Animals were sacrificed at various times after drug administration. MPTP produced no significant increase in ROS nor decreases in DA or HVA concentrations in the striatum of the younger mice. However, DOPAC concentrations were significantly decreased from 15–120 min after drug administration. In the older mice, MPTP caused significant increases in ROS from the beginning to the end of the study period. DA concentrations were decreased from 60 min onward. DOPAC concentrations were decreased significantly after 15–120 min while HVA concentrations were significantly increased after 60 and 120 min. These data demonstrate that in older mice, a single dose of MPTP can cause increases of ROS which were associated with subsequent decreases in DA concentrations. Younger mice were not similarly affected. These results suggest that MPTP induced neurotoxicity is age‐dependent and may be mediated by oxidative stress. ©1994 Wiley‐Lisa, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.