bluuebunny/crossref_metadata_2025_split huggingface dataset:
The paradoxical effect of NMDA receptor stimulation on electrical activity of the sensorimotor cortex in freely behaving rats: Analysis by combined EEG‐intracerebral microdialysis
Authors: Ludvig Nandor , Mishra Pravin K. , Yan Qing‐Shan , Lasley Stephen M. , Burger Robert L. , Jobe Phillip C. 
Published: December 2004

AbstractThis study was designed to determine the effects of N‐methyl‐D‐aspartate (NMDA) receptor stimulation on the electrical activity of neocortex in freely behaving rats. Electroencephalogram (EEG) recording and intracerebral microdialysis were conducted simultaneously in the same site of the sensorimotor cortex, where the basal extracellular concentrations of aspartate and glutamate were 2.1 ± 0.7 m̈M and 11.5 ± 2.4 m̈M, respectively. Microdialysis with NMDA solutions (ranging from 10.0 m̈M to 10.0 mM) reduced the amplitude of the EEG activity and decreased the power of all frequency bands, with a virtual elimination of the high frequency waves, in a dose‐dependent manner. These EEG changes were reversed after washing out the drug from the microdialysis fluid, and could be effectively antagonized with the competitive NMDA receptor antagonist DL‐2‐amino‐5‐phosphonovalerate. Remarkably, the NMDA actions were not associated with epileptiform behavioral or electrographic events. Control studies demonstrated that in the same experimental conditions, cholinergic receptor agonist carbachol caused seizures, and microdialysis with NMDA in the hippocampus readily induced epileptiform spikes. Our study shows that NMDA receptor stimulation in the rat sensorimotor cortex, although excitatory at synaptic level, can depress the local EEG activity. This may indicate that the NMDA receptor‐mediated signals are processed by the neocortical network in a different way than by many other brain circuitries including hippocampus. © 1992 Wiley‐Liss, Inc.
A review of the role of anti‐opioid peptides in morphine tolerance and dependence
Authors: Rothman Richard B. 
Published: December 2004

AbstractStudies on the mechanisms of tolerance and dependence have mostly focused on changes at the receptor level. These experiments, conducted with model systems ranging from clonal cell lines to whole animals, have identified a number of important adaptive mechanisms which occur at the receptor level. However, none of these adaptive mechanisms can completely account for the phenomena which serve to define the state of morphine tolerance and dependence, especially the observation that as an animal becomes more tolerant to morphine, less naloxone is required to trigger withdrawal. The data reviewed in this paper provide strong support for the hypothesis that the brain synthesizes and secretes neuropeptides which act as part of a homeostatic system to attenuate the effects of morphine and endogenous opioid peptides. According to this model, administration of morphine releases anti‐opioid peptides (AOP), which then attenuate the effects of morphine. As more morphine is given, more AOP are released, thereby producing tolerance to the effects of morphine. Cessation of morphine administration, or administration of naloxone, produces a relative excess of anti‐opioid, which is in part responsible for the withdrawal syndrome. Since endogenous and exogenous antagonists might together produce synergistic effects, less naloxone might be required to trigger withdrawal in the presence of higher levels of AOPs. Although the study of AOP is in its infancy, a deeper understanding of the central nervous system (CNS) anti‐opioid systems may lead to new treatments for chronic pain, substance abuse, and psychiatric disorders. © 1992 Wiley‐Liss, Inc.
Serotonergic signalling between thyroid cells: Protein kinase C and 5‐HT2 receptors in the secretion and action of serotonin
Authors: Tamir Hadassah , Hsiung Shu‐Chi , Yu Pei‐Ying Y. , Liu Kuo‐Peing , Adlersberg Mella , Nunez Eladio A. , Gershon Michael D. 
Published: December 2004

AbstractParafollicular (PF) cells of the thyroid gland are neural crest derivatives, which costore the neurotransmitter, 5‐hydroxytryptamine (5‐HT) with calcitonin. PF cells are located adjacent to follicular (F) cells within the basement membrane of thyroid follicles. It has been proposed that 5‐HT serves an intercellular signalling function in the thyroid and that F cells are its target. This proposal was tested by using cell lines derived from PF (medullary thyroid carcinoma [MTC]) and F (FRTL‐5) cells to study the mechanisms that mediate the secretion and action of 5‐HT. Secretion of 5‐HT by MTC cells was evoked by thyroid stimulating hormone, thyrotropin (TSH), elevated extracellular calcium (↑[Ca2+]e), or by agents that increase intracellular cAMP (↑[cAMP]i). When protein kinase C (PKC) was down‐regulated by prolonged treatment of MTC cells with phorbol 12‐myristate 13‐acetate (PMA), or PKC was inhibited by staurosporin, the TSH‐or PMA‐evoked secretion of 5‐HT was blocked; however, interference with PKC function did not affect 5‐HT secretion evoked by ↑ [Ca2+]e or ↑ [cAMP]i. In the putative targets, FRTL‐5 cells, 5‐HT increased the turnover of phosphoinositides (PI), cytosolic calcium (↑[Ca2+]i), ↑[cAMP]i, and biphasically modified the effect of TSH on cAMP. All of these 5‐HT effects were inhibited by 5‐HT2 receptor antagonists (spiperone and ketanserin) and by pertussis toxin (PTx), suggesting that the actions of 5‐HT are mediated by 5‐HT2 receptors, which are coupled to a G protein. This suggestion was supported by the following additional observations: FRTL‐5 membranes bound the 5‐HT2 agonist, [125I]2,5‐dimethoxy‐4‐iodophenylisopropylamine ([125I]‐DOI), and anti‐idiotypic anti‐bodies, which recognize 5‐HT2 receptors. [125I]‐DOI binding was inhibited by guanosine‐5′‐O‐(3‐thiotriphosphate) (GTP‐γ‐S) and the antibodies were displaced by spiperone. Data are consistent with the hypothesis that 5‐HT serves as a PF to F cell messenger. © 1992 Wiley‐Liss, Inc.
Metabolic mapping of the synergism between MK‐801 and SKF 38393 in rats with unilateral lesions of the dopaminergic nigrostriatal pathway
Authors: Pontieri Francesco E. , Morelli Micaela , Orzi Francesco , Terenzi Riccardo , Di Chira Gaetano 
Published: December 2004

AbstractIn rats with a unilateral lesion of the dopaminergic nigrostriatal pathway with 6‐hydroxydopamine, blockade of N‐methyl‐D‐aspartate receptors by MK‐801 strongly potentiated the turning behavior induced by D‐1 receptor stimulation. To determine the functional consequences of such positive interaction we measured the local rates of cerebral glucose utilization (ICMRglc) in lesioned rats treated with MK‐801 (0.1mg/kg) and the D‐1 agonist SKF 38393 (1.5 mg/kg), either alone or in combination. Treatment with each drug separately did not induce any substantial change in ICMRglc besides an increase in the metabolic activity of the dorsomedial caudate and entopeduncular nucleus (EP) of the lesioned side of MK‐801 treated rats, as compared to the same side of lesioned rats treated with vehicle. Combined administration of MK‐801 + SKF 38393 increased ICMRglc in the EP (+77%) and in the substantia nigra pars reticulata (SNr) (+30%) of the lesioned side as compared with the intact side, while it decreased ICMRglc in the lateral habenula (−26%). These changes were also significant when compared to the lesioned side of vehicle treated rats. The results suggest that while the caudate putamen might be the primary site of MK‐801 and SKF 38393 positive interaction, the EP and SNr are the striatal efferent areas where this positive interaction is expressed. © 1992 Wiley‐Liss, Inc.
Non 5‐HT1A/5‐HT1C[3H]5‐HT binding sites in the hamster, opossum, and rabbit brain show similar regional distribution but different sensitivity to β‐adrenoceptor antagonists
Authors: Waeber Christian , Palacios José M. 
Published: December 2004

AbstractWe have used receptor autoradiography to investigate the distribution and pharmacological profile of non 5‐HT1A/5‐HT1C[3H]5‐hydroxytryptamine binding sites in the brain of rabbits, hamsters and opossums. These data were compared to those found under similar conditions in the brain of rats and guinea pigs, species which are known to possess 5‐HT1B and 5‐HT1D receptors, respectively. In the presence of 100 nM 8‐OH‐DPAT and mesulergine, the regional distribution of [3H]5‐hydroxytryptamine binding sites was very similar in the brain of all species investigated; densest labelling was observed in the globus pallidus, substantia nigra and superior colliculus. In all species, 5‐carboxamidotryptamine competed for the labelled sites in a biphasic manner and metergoline displayed a subnanomolar affinity. In contrast, the β‐adrenoceptor blocking agents (−)propranolol, (−)pindolol, and (±)SDZ 21009 were potent displacers only in the rat, hamster and opossum brains. These data indicate that non 5‐HT1A/5‐HT1C[3H]5‐HT binding sites display a high affinity for these agents in a particular rodent suborder as well as in opossum, a phylogenetically unrelated species. © 1992 Wiley‐Liss, Inc.
Dopaminergic regulation of cortical acetylcholine release
Authors: Day Jamie , Fibiger Hans C. 
Published: December 2004

AbstractThe extent to which the activity of basal forebrain cholinergic neurons is influenced by dopamine (DA) was investigated using in vivo microdialysis of cortical acetylcholine (ACh). Systemic administration of the DA receptor agonist apomorphine significantly increased dialysate concentrations of ACh. Systemic, but not local, administration of d‐amphetamine produced similar effects. Both D1 (SCH 23390) and D2 (haloperidol, raclopride) DA receptor antagonists attenuated the amphetamine‐induced increase in cortical ACh release; however, only the D1 antagonist significantly reduced basal output of cortical ACh. These findings suggest that the activity of cortically projecting cholinergic neurons in the nucleus basalis is regulated in an excitatory manner by central dopaminergic neurons and that both D1 and D2 receptors are involved. © 1992 Wiley‐Liss, Inc.
Interaction of amfonelic acid with antipsychotic drugs on dopaminergic neurons
Authors: Gudelsky Gary A. , Nwajei E. Ewanzani , Defife Kristen , Nash J. Frank 
Published: December 2004

AbstractThe effects of two inhibitors of dopamine (DA) reuptake, amfonelic acid and GBR 12909, on the clozapine‐and haloperidol‐induced increases in DA synthesis, release, and metabolism were investigated in the rat. In the striatum, as well as in the nucleus accumbens, the haloperidol‐induced increase in tissue concentrations of dihydroxyphenylacetic acid (DOPAC) or the accumulation of dihydroxyphenylalanine (DOPA) was potentiated or unaltered, respectively, in rats treated with amfonelic acid. In contrast, amfonelic acid attenuated the stimulatory effects of clozapine on DOPAC concentrations and DOPA accumulation in both brain regions. GBR 12909 also differentially affected the haloperidol‐ and clozapine‐induced increases in DOPAC concentrations. However, the clozapine‐induced increase in DOPA accumulation in the median eminence was not significantly altered by treatment with amfonelic acid. The haloperidol‐induced increase in the extracellular concentrations of DA and DOPAC in the striatum also was potentiated by amfonelic acid, whereas the increase elicited by clozapine was suppressed. The increase in extracellular DA produced by the administration of morphine or the coadministration of ritanserin, a 5‐HT2 antagonist, and haloperidol also was potentiated by amfonelic acid. The ability of amfonelic acid to distinguish between the actions of clozapine and haloperidol on nigrostriatal and mesocorticolimbic DA neurons does not appear to be related to differences in the effects of the drugs on DA autoreceptors or 5‐HT2 receptors. Moreover, the mechanism, through which clozapine activates tuberoinfundibular DA neurons may differ from that which is involved in the activation of nigrostriatal or mesocorticolimbic DA neurons. © 1992 Wiley‐Liss, Inc.
Evaluation of [3H]paroxetine as an in vivo ligand for serotonin uptake sites: A quantitative autoradiographic study in the rat brain
Authors: Biegon Anat , Mathis Chester 
Published: December 2004

AbstractParoxetine, a selective inhibitor of serotonin uptake and an antidepressant, was used in conjunction with quantitative ex vivo autoradiography to study the feasibility of imaging serotonin terminals in the living brain. Tritiated paroxetine was injected in the rat tail vein, and the brain was processed for quantitative autoradiography 3 hours later. Animals received either [3H]paroxetine alone (100 μCi/animal) or a mixture of labeled paroxetine (100 μCi) and an excess of unlabeled drug (0.5 or 2 mg/kg intravenously [i.v.]). Computerized image analysis of the resulting autoradiograms revealed high densities of radioactivity in brain regions known to contain high densities of serotonergic terminals and high specific binding of [3H]paroxetine in vitro, such as the raphe nuclei, interpeduncular nucleus, basolateral amygdala, substantia nigra, and some hypothalamic nuclei. Radioactivity uptake in these brain regions was effectively blocked (50‐72%) by coadministration of excess unlabeled paroxetine. However, cortical and hippocampal binding of paroxetine in vivo was moderately high, in contrast to the relatively sparse serotonergic innervation in these regions. Only a relatively small proportion of cortical and hippocampal binding (20‐40%) could be blocked by excess unlabeled paroxetine, indicating that most of the radioactivity in these regions is not associated with serotonin terminals or uptake sites. The usefulness of [3H]paroxetine as an in vivo ligand for imaging serotonin terminals in the human brain is limited by these nonserotonergic binding sites. © 1993 Wiley‐Liss, Inc.
Day/night differences in D1 but not D2 DA receptor protection from EEDQ denaturation in rats treated with continuous cocaine
Authors: Burger Lynn Y. , Martin‐Iverson Mathew T. 
Published: December 2004

AbstractThe effect of chronic cocaine administration on the in vivo occupation of dopamine (DA) receptor subtypes was examined using the irreversible receptor blocker N‐ethoxycarbonyl‐2‐ethoxy‐1, 2‐dihydroquinoline (EEDQ). Rats were given continuous infusions of cocaine (vehicle, 2.5, 7.5, or 22.5 mg/day) via subcutaneous implants of Alzet osmotic minipumps for 14 days. Some groups were also given the D1 antagonist SCH 23390 and/or the D2 antagonist raclopride for this same time period. DA receptor binding techniques were used 24 hours post‐EEDQ injection (Day 15, 5 mg/kg, intraperitoneally [ip]) in order to examine changes in D1 and D2 receptor densities in the striatum. Half of the rats were killed in the day with the other half killed at night in order to examine day/night differences in the effects of cocaine treatment. Results showed that chronic cocaine increased the protection of D1 receptors from EEDQ inactivation in a dosedependent fashion during the day, and decreased D1 protection from EEDQ at night. Since EEDQ has a low affinity for the DA receptor relative to endogenous DA or the exogenous ligands in this study, only receptors that are vacant are inactivated thereby allowing for an estimate of DA receptor occupation in vivo. Cocaine can therefore be said to increase D1 receptor occupation by DA in vivo during the day and decrease it at night. Coadministration of the DA antagonists eliminated this cocaine‐induced day/night difference and, in the case of the D1 antagonist, produced opposite D1 receptor effects when administered alone. Chronic SCH 23390 treatment protected D1 receptors from EEDQ denaturation while D2 receptors were protected by chronic raclopride. In addition, raclopride was found to affect the affinity of both the D1 and the D2 receptors to the [3H]SCH 23390 and [3H] spiperone ligands, respectively. Since no day/night differences were found in D2 receptor density with respect to chronic cocaine treatment these findings have implications for a phasic D1/tonic D2 receptor hypothesis such that cocaine treatment selectively alters the level of DA at sites containing D1 receptors with differential effects depending on the day/night cycle. © 1993 Wiley‐Liss, Inc.
Decamethonium is a partial agonist at the nicotinic acetylcholine receptor
Authors: Liu Yi , Dilger James P. 
Published: December 2004

AbstractThe efficacy of decamethonium as an agonist at the nicotinic acetylcholine receptor has never been determined. Here, we demonstrate how patch clamp recording during rapid perfusion of agonists to outside‐out patches from BC3H‐1 cells can be used to provide an unambiguous estimate of the efficacy of decamethonium. First, we obtain the decamethonium concentration‐response relationship between 10 and 1,000 μM decamethonium. The maximum channel open probability is small (<0.02) and occurs at about 100 μM. This suggests two alternative explanations: decamethonium is a poor agonist or decamethonium is an efficacious agonist but a potent channel blocker. To distinguish between these alternatives, we perfuse mixtures of decamethonium and acetylcholine to generate acetylcholine concentration‐response curves in the presence of 30, 100, and 1,000 μM decamethonium. We use a model for activation and block of the acetylcholine receptor by both agonists to fit these data and determine the binding affinity, efficacy, and blocking affinity of decamethonium. We conclude that the efficacy of decamethonium is low 0.016. Decamethonium is a true partial agonist. © 1993 Wiley‐Liss, Inc.
Ventral tegmental self‐stimulation selectively induces opioid peptide release in rat CNS
Authors: Stein Elliot A. 
Published: December 2004

AbstractIntracranial self‐stimulation (ICS) is thought to activate neuronal systems involved in processing natural reinforcing agents. Metabolic mapping studies have previously demonstrated a subset of CNS structures specifically engaged by ICS in animals receiving stimulation actively vs. passively. Since opiates are known to enhance JCS behavior and presumably its reinforcing properties, the current study addressed the question of the role of opioid peptides as mediators of ICS. Rats were trained on a fixed ration (FR) 20 schedule of responding maintained by ICS. Following response stabilization, rats were assigned either to an active or a corresponding yoked stimulation group at 1 of 2 schedules of reinforcement (i. e., FR1‐YFR1, FR20‐YFR20, or sedentary control), and opioid peptide release was inferred from in vivo receptor occupancy. Autoradiographic analyses identified 3 groups of structures. Treatment‐induced alterations in occupancy were seen in the medial dorsal nucleus of the thalamus, basolateral amygdala, ventral pallidum, medial habenula, dorsal raphe, posterior hypothalamus, substantia nigra pars compacta, agranular preinsular cortex, and zona incerta. Depending upon the structure, peptide release was dependent upon stimulus contingency (active vs. yoked) and/or schedule (FR1 vs. FR20). Evidence for ICS‐induced inhibition of peptide release was found in the habenula and preinsular cortex. Nine additional structures, all components of, or receiving projections from, the limbic system, revealed complex interactions between ICS treatment and the electrode side. Finally, a widespread ipsilateral increase in receptor binding was seen rostrally from the cingulate, olfactory tubercle, and nucleus accumbens, along the lateral hypothalamus and hippocampus, and extending caudally to the substantia nigra and ventral tegmentum. These later effects appear to be related to stimulation‐induced changes in blood flow and subsequent ligant presentation increases. Collectively, these data point towards the ability of rewarding brain stimulation to activate discrete neuronal opioid systems contingent upon specific behavioral as well as stimulus conditions. © 1993 Wiley‐Liss, Inc.
Light and electron microscopic localization of calcitonin gene‐related peptide immunoreactivity in lamina II of the feline trigeminal pars caudalis/medullary dorsal horn: A qualitative study
Authors: Henry Michael A. , Nousek‐Goebl Nancy A. , Westrum Lesnick E. 
Published: December 2004

AbstractCalcitonin gene‐related peptide (CGRP) is a neuropeptide that is associated with a subset of primary afferent fibers and appears to have a role in nociception. The purpose of the present study was to perform a qualitative light, and especially electron microscopic (LM and EM), examination of CGRP‐immunoreactivity (IR) within lamina II (substantia gelatinosa) of the feline pars caudalis/medullary dorsal horn (PC/MDH) of the spinal trigeminal nucleus. The LM investigation revealed massive CGRP‐IR within lamina II outer, with fewer fibers that traversed lamina II inner. The EM preparations showed CGRP‐IR in small, thinly myelinated and unmyelinated axons, preterminal axons, and in axon terminals that formed asymmetric synaptic contacts onto small dendritic profiles. The terminals with CGRP‐IR were often the central element within glomeruli, where the terminal usually formed 2 or more asymmetric synaptic specializations onto 1 or more dendrites. Many of these postsynaptic dendrites contained synaptic vesicles. Other profiles were seen forming presynaptic contacts onto the terminal with CGRP‐IR, and these profiles most likely represent presynaptic dendrites and/or other axon terminals of intrinsic origin. The synaptic association of terminals showing CGRP‐IR with vesicle‐containing dendrites, presynaptic dendrites, and/or other axon terminals suggests that terminals with CGRP‐IR are especially susceptible to modulation. © 1993 Wiley‐Liss, Inc.
MK‐801, phencyclidine (PCP), and PCP‐like drugs increase burst firing in rat A10 dopamine neurons: Comparison to competitive NMDA antagonists
Authors: French Edward D. , Mura Anna , Wang Ting 
Published: December 2004

AbstractExtracellular single‐unit recordings were used to assess the effects of PCP and PCP‐like drugs (MK‐801 and TCP) on the burst firing of ventral tegmental A10 dopamine neurons in the rat. The effects of these noncompetitive N‐methyl‐D‐aspartate (NMDA) receptor antagonists were compared to the potent and competitive NMDA antagonists CGS 19755 and (±)CPP, and to BTCP, a PCP‐derivative possessing little affinity for the PCP binding site within the ion channel gated by NMDA. PCP, MK‐801, and TCP produced dose‐dependent increases in the firing rate, which were accompanied by increases in the amount of burst activity, the number of action potentials within a burst, and the conversion of nonbursty cells to bursty. However, the coefficient of variation, a measure of the regularity of firing, was not significantly altered. These predominately excitatory effects contrast with the inhibition of firing, decrease in bursting, and regularization of pattern produced by BTCP. CGS 19755 and (±) CPP failed to alter any of the measured parameters. Thus, the increase in firing rate and amount of burst activity of dopamine neurons produced by PCP and PCP‐like drugs, and the resultant hyperdopaminergia within the mesolimbic‐mesocortical regions, could underlie the psychotomimetic properties of these compounds. Moreover, this effect would not appear to be related to a loss of activity at the NMDA recognition site, as evidenced by the lack of effect of the competitive NMDA antagonists. © 1993 Wiley‐Liss, Inc.