bluuebunny/crossref_metadata_2025_split huggingface dataset:
A single exposure to morphine induces long‐lasting behavioural and neurochemical sensitization in rats
Authors: Vanderschuren Louk J. M. J. , De Vries Taco J. , Wardeh George , Hogenboom François A. C. M. , Schoffelmeer Anton N. M. 
Published: March 2003

AbstractRepeated exposure to drugs of abuse causes persistent behavioural sensitization and associated adaptations in striatal neurotransmission, which is thought to play an important role in certain aspects of drug addiction. Remarkably, even a single exposure to psychostimulant drugs such as amphetamine or cocaine can be sufficient to elicit long‐lasting sensitization. The present study was designed to evaluate whether long‐lasting behavioural and neurochemical sensitization can also be evoked by a single exposure to morphine, an opiate drug of abuse. Rats were pretreated once with morphine (2, 10 or 30 mg/kg). Three weeks later, the locomotor effects of morphine and amphetamine, as well as the electrically evoked release of [3H]dopamine and [14C]acetylcholine from slices of nucleus accumbens and caudate–putamen, was assessed. In morphine‐pretreated rats, the psychomotor effects of morphine and amphetamine were sensitized. In addition, the electrically evoked release of [3H]dopamine and [14C]acetylcholine was augmented in slices of nucleus accumbens and caudate–putamen from morphine‐pretreated animals. Although the sensitization of the locomotor effect of morphine was less profound than previously observed after repeated intermittent morphine treatment, the enduring behavioural and neurochemical consequences of a single and repeated intermittent morphine treatment appear to be highly comparable. We therefore conclude that a single exposure to morphine induces long‐lasting behavioural sensitization and associated neuroadaptations.
Modulation of the synchronization between cells in visual cortex by contextual targets
Authors: Bretzner Fréderic , Aïtoubah Jamila , Shumikhina Svetlana , Tan Yao‐Fang , Molotchnikoff Stéphane 
Published: March 2003

AbstractIt has been suggested that synchronization of action potentials encodes diverse features of a single image. However, properties of the synchronization, which occurs on a time scale of ≈ 1–5 ms, are still poorly understood. We have tested the modulation of synchronization by manipulating the contextual targets introduced in the surround of the receptive field. Experiments were carried out on anaesthetized cats prepared for multiunit and single‐cell recordings in area 17. Initially, a patch of sine‐wave drifting grating was positioned over the overlapping receptive fields of several neurons. If this coherent motion produced a significant synchronization in cross‐correlograms, contextual targets were added. The first contextual stimuli were two sine‐wave patches placed above and below the central compound receptive field. Only the contrast of contextual targets changed. Results show that the larger the differential contrast the higher the synchronization. The second contextual stimulus was a lateral shift of a sine‐wave patch. Data show that the wider the distance between the central and peripheral patches the better the synchronization. Furthermore, results suggest that the synchrony pattern computed by cross correlating multiunit recordings from two sites differs when the cross correlation is carried out between individual units belonging to each multiunit recording. Together with our previous results it appears that synchronization is stimulus dependent and its strength increases with larger disparities included in the whole stimulating image.
Orexins (hypocretins) directly excite tuberomammillary neurons
Authors: Bayer Laurence , Eggermann Emmanuel , Serafin Mauro , Saint‐Mleux Benoît , Machard D. , Jones Barbara , Mühlethaler Michel 
Published: March 2003

AbstractWakefulness has recently been shown to depend upon the newly identified orexin (or hypocretin) neuropeptides by the findings that alteration in their precursor protein, their receptors or the neurons that produce them leads to the sleep disorder narcolepsy in both animals and humans. The questions of how and where these brain peptides act to maintain wakefulness remain unresolved. The purpose of the present study was to determine whether the orexins could directly affect hypothalamic histaminergic neurons, which are known to contribute to the state of wakefulness by their diffuse projections through the brain. Using brain slices, we recorded in the ventral tuberomammillary nuclei from neurons identified as histaminergic on the basis of their previously described morphological and electrophysiological characteristics and found that they were depolarized and excited by the orexins through a direct postsynaptic action. We then compared the depolarizing effect of orexin A and B and found that they were equally effective upon these cells. This latter finding suggests that the effect of orexins is mediated by orexin type 2 receptors, which are those lacking in narcoleptic dogs. Our results therefore show that the histaminergic neurons of the tuberomammillary nuclei represent an important target for the orexin system in the maintenance of wakefulness.
Altered hippocampal gene expression prior to the onset of spontaneous seizures in the rat post‐status epilepticus model
Authors: Hendriksen H. , Datson Nicole A. , Ghijsen Wim E. J. M. , Van Vliet Erwin A. , Da Silva Fernando H. Lopes , Gorter Jan A. , Vreugdenhil Erno 
Published: March 2003

AbstractNeuronal loss, gliosis and axonal sprouting in the hippocampal formation are characteristics of the syndrome of mesial temporal sclerosis (MTS). In the post‐status epilepticus (SE) rat model of spontaneous seizures these features of the MTS syndrome can be reproduced. To get a global view of the changes in gene expression in the hippocampus we applied serial analysis of gene expression (SAGE) during the early phase of epileptogenesis (latent period), prior to the onset of the first spontaneous seizure. A total of 10 000 SAGE tags were analyzed per experimental group, resulting in 5053 (SE) and 5918 (control group) unique tags (genes), each representing a specific mRNA transcript. Of these, 92 genes were differentially expressed in the hippocampus of post‐SE rats in comparison to controls. These genes appeared to be mainly associated with ribosomal proteins, protein processing, axonal growth and glial proliferation proteins. Verification of two of the differentially expressed genes by in situ hybridization confirmed the changes found by SAGE. Histological analysis of hippocampal sections obtained 8 days after SE showed extensive cell loss, mossy fibre sprouting and gliosis in hippocampal sub regions. This study identifies new high‐abundant genes that may play an important role in post‐SE epileptogenesis.
Cystatin C, a cysteine protease inhibitor, is persistently up‐regulated in neurons and glia in a rat model for mesial temporal lobe epilepsy
Authors: Aronica Eleonora , Van Vliet Erwin A. , Hendriksen Erik , Troost Dirk , Lopes da Silva Fernando H. , Gorter Jan A. 
Published: March 2003

AbstractCystatin C (CSTC), a cysteine protease inhibitor, has been implicated in the processes of neuronal degeneration and repair of the nervous system. Using serial analysis of gene expression (SAGE), we recently identified CSTC as one of the genes that are overexpressed after electrically induced status epilepticus (SE). In the present study, Western blot analysis extended the SAGE results, showing increased CSTC protein in the hippocampus and entorhinal cortex. Immunocytochemistry revealed an increase in CSTC expression in glial cells, which was first apparent 24 h after onset of SE, and persisted for at least 3 months. Double immunolabelling confirmed that both reactive astrocytes, and activated microglia were CSTC immunopositive. Within the hippocampus, up‐regulation was also observed in neuronal cells within one day after SE. Up‐regulation was still present in hippocampal pyramidal cells and surviving interneurons of chronic epileptic rats (3–8 months post‐SE). This study demonstrates that status epilepticus leads to a widespread and persistent up‐regulation of CSTC in the hippocampus and entorhinal cortex, which may represent an intrinsic neuroprotective mechanism in the course of epileptogenesis that may counteract progression of the disease.
Histamine H3 receptor‐mediated impairment of contextual fear conditioning and in‐vivo inhibition of cholinergic transmission in the rat basolateral amygdala
Authors: Passani M. Beatrice , Cangioli Iacopo , Baldi Elisabetta , Bucherelli Corrado , Mannaioni Pier Francesco , Blandina Patrizio 
Published: March 2003

AbstractWe investigated the effects of agents acting at histamine receptors on both, spontaneous release of ACh from the basolateral amygdala (BLA) of freely moving rats, and fear conditioning. Extensive evidence suggests that the effects of histamine on cognition might be explained by the modulation of cholinergic systems. Using the microdialysis technique in freely moving rats, we demonstrated that perfusion of the BLA with histaminergic compounds modulates the spontaneous release of ACh. The addition of 100 mm KCl to the perfusion medium strongly stimulated ACh release, whereas, 0.5 µm tetrodotoxin (TTX) inhibited spontaneous ACh release by more than 50%. Histaminergic H3 antagonists (ciproxifan, clobenpropit and thioperamide), directly administered to the BLA, decreased ACh spontaneous release, an effect fully antagonized by the simultaneous perfusion of the BLA with cimetidine, an H2 antagonist. Local administration of cimetidine alone increased ACh spontaneous release slightly, but significantly. Conversely, the administration of H1 antagonists failed to alter ACh spontaneous release. Rats receiving intra‐BLA, bilateral injections of the H3 antagonists at doses similar to those inhibiting ACh spontaneous release, immediately after contextual fear conditioning, showed memory consolidation impairment of contextual fear conditioning. Post‐training, bilateral injections of 50 µg scopolamine also had an adverse effect on memory retention. These observations provide the first evidence that histamine receptors are involved in the modulation of cholinergic tone in the amygdala and in the consolidation of fear conditioning.
Hypothalamic–pituitary–adrenal axis function and corticosterone receptor expression in behaviourally characterized young and aged Long–Evans rats
Authors: Bizon Jennifer L. , Helm Katherine A. , Han Jung‐Soo , Chun Hyun‐Ja , Pucilowska Jolanta , Lund Pauline Kay , Gallagher Michela 
Published: March 2003

AbstractIn the current investigation, hypothalamic–pituitary–adrenal (HPA) axis function was examined in young and aged male Long‐Evans rats that were initially assessed on a version of the Morris water maze sensitive to cognitive impairment during ageing. In behaviourally characterized rats, a 1‐h restraint stress paradigm revealed that plasma corticosterone concentrations in aged cognitively impaired rats took significantly longer to return to baseline following the stressor than did those in young or aged cognitively unimpaired rats. No differences in basal or peak plasma corticosterone concentrations, however, were observed between young or aged rats, irrespective of cognitive status. Using ribonuclease protection assays and in situ hybridization, we evaluated mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mRNA abundance in young and aged rats characterized on the spatial task. Abundance of MR mRNA was decreased as a function of age in stratum granulosum but not hippocampus proper, and the decrease in MR mRNA was largely unrelated to cognitive status. However, GR mRNA was significantly reduced in several hippocampal subfields (i.e. stratum granulosum and temporal hippocampus proper) and other related cortical structures (medial prefrontal and olfactory regions) of aged cognitively impaired rats compared to either young or aged cognitively unimpaired cohorts, and was significantly correlated with spatial learning ability among the aged rats in each of these brain regions. In agreement with previous stereological data from this ageing model, no changes were detected in neuron density in the hippocampus of the rats used in the in situ hybridization analysis. These data are the first to describe a coordinated decrease in GR mRNA in a functional brain system including hippocampus and related cortical areas that occurs in tandem with impairments of the HPA response to stress and cognitive decline in ageing.
Discharge patterns of neurons in the medial pontobulbar reticular formation during fictive mastication in the rabbit
Authors: Westberg K.‐G. , Scott G. , Olsson K. Å. , Lund J. P. 
Published: March 2003

AbstractIn this study, we describe functional characteristics of neurons forming networks generating oral ingestive motor behaviours. Neurons in medial reticular nuclei on the right side of the brainstem between the trigeminal and hypoglossal motor nuclei were recorded in anaesthetized and paralysed rabbits during two types of masticatory‐like motor patterns induced by electrical stimulation of the left (contralateral) or right (ipsilateral) cortical masticatory areas. Sixty‐seven neurons in nucleus reticularis pontis caudalis (nPontc), nucleus reticularis parvocellularis (nParv), and nucleus reticularis gigantocellularis (Rgc) were studied. These were classified as phasic or tonic depending on their firing pattern during the fictive jaw movement cycle. Phasic neurons located in the dorsal part of nPontc were active during the jaw opening phase, whilst those in dorsal nParv tended to fire during the closing phase. In most neurons, burst duration and firing frequency changed between the two motor patterns, but there was little change in phase of firing. Tonic units were mainly recorded in the ventral half of nPontc, and at the junction between Rgc and caudal nParv. Cortical inputs with short latency from the contralateral masticatory area were more frequent in phasic (82%) than tonic (44%) neurons, whilst inputs from the ipsilateral cortex were equal in the two subgroups (57% and 56%). Phasic neurons had significantly shorter mean contralateral than ipsilateral cortical latencies, whilst there was no difference among tonic neurons. Intra‐ and perioral primary afferent inputs activated both types of neurons at oligo‐synaptic latencies. Our results show that subpopulations of neurons in medial reticular nuclei extending from the caudal part of the trigeminal motor nucleus to the rostral third of the hypoglossal motor nucleus are active during the fictive masticatory motor behaviour. Unlike masticatory neurons in the lateral tegmentum, the medial subpopulations are spatially organized according to discharge pattern.
Differential sensitivity of medium‐ and large‐sized striatal neurons to NMDA but not kainate receptor activation in the rat
Authors: Cepeda Carlos , Itri Jason N. , Flores‐Hernández Jorge , Hurst Raymond S. , Calvert Christopher R. , Levine Michael S. 
Published: March 2003

AbstractInfrared videomicroscopy and differential interference contrast optics were used to identify medium‐ and large‐sized neurons in striatal slices from young rats. Whole‐cell patch‐clamp recordings were obtained to compare membrane currents evoked by application of N‐methyl‐d‐aspartate (NMDA) and kainate. Inward currents and current densities induced by NMDA were significantly smaller in large‐ than in medium‐sized striatal neurons. The negative slope conductance for NMDA currents was greater in medium‐ than in large‐sized neurons and more depolarization was required to remove the Mg2+ blockade. In contrast, currents induced by kainate were significantly greater in large‐sized neurons whilst current densities were approximately equal in both cell types. Spontaneous excitatory postsynaptic currents occurred frequently in medium‐sized neurons but were relatively infrequent in large‐sized neurons. Excitatory postsynaptic currents evoked by electrical stimulation were smaller in large‐ than in medium‐sized neurons. A final set of experiments assessed a functional consequence of the differential sensitivity of medium‐ and large‐sized neurons to NMDA. Cell swelling was used to examine changes in somatic area in both neuronal types after prolonged application of NMDA or kainate. NMDA produced a time‐dependent increase in somatic area in medium‐sized neurons whilst it produced only minimal changes in large interneurons. In contrast, application of kainate produced significant swelling in both medium‐ and large‐sized cells. We hypothesize that reduced sensitivity to NMDA may be due to variations in receptor subunit composition and/or the relative density of receptors in the two cell types. These findings help define the conditions that put neurons at risk for excitotoxic damage in neurological disorders.
Neither major depression nor glucocorticoid treatment affects the cellular integrity of the human hippocampus
Authors: Müller Marianne B. , Lucassen Paul J. , Yassouridis Alexander , Hoogendijk Witte J. G. , Holsboer Florian , Swaab Dick F. 
Published: March 2003

AbstractIn major depression, decreased hippocampal volume has been attributed to hypercortisolemia, a frequent sign of the disorder, because in animals an excess of corticosteroids has led to dendritic atrophy, astrogliosis and loss of neurons in this brain region. The present study is the first to investigate the structural integrity of the human hippocampus in major depression and following glucocorticoid treatment. Post‐mortem hippocampal tissue from 15 patients who had had major depression or bipolar affective disorder, 10 patients who had been treated with glucocorticoids and 16 controls was assessed using haematoxylin‐eosin, Nissl and Bodian staining. The patterns of reactive astrogliosis (glial fibrillary acidic protein, GFAP), synaptic density (synaptophysin), synaptic reorganization (growth‐associated protein B‐50) and early signs of Alzheimer's disease (Alz‐50) were examined immunocytochemically. Multivariate analysis, with the patients' age, tissue fixation time and postmortem delay as covariates, was performed. There was no evidence of neuronal cell loss or other major morphological alterations in any of the groups, nor was there a significant change in the distribution pattern of synaptophysin or Alz‐50. Changes in B‐50 and GFAP staining were observed in the steroid‐treated and depressed patients in areas CA1 and CA2 only. The human hippocampus in major depression and after glucocorticoid treatment does not reveal any major morphological changes or signs of neuronal cell death, but does show subtle alterations in B‐50 and GFAP expression in selected parts of the pyramidal cell layer.
Change blindness and time to consciousness
Authors: Niedeggen Michael , Wichmann Petra , Stoerig Petra 
Published: March 2003

AbstractDetection of changes in a visual scene can be substantially delayed when the original and the modified image are separated by a brief screen flicker. We used this phenomenon of ‘change blindness’ to find when the brain detects the mismatch in relation to when the observer reports it, and whether changes in identity and position are processed similarly. Event‐related brain potentials (ERPs) recorded while the subjects searched for the change in alternating series of images showed that the epoch during which they indicated detection was characterized by a marked positivity from 300 to 700 ms. Analysis of data from image presentations preceding the subjects' response revealed a similar but smaller ERP positivity one (identity) or even two (position) epochs before detection. As each epoch lasted 1500 ms, the brain may register a change as early as 3000 ms before the observer.
Developmental expression of the calcium release channels during early neurogenesis of the mouse cerebral cortex
Authors: Faure Anne‐Valérie , Grunwald Didier , Moutin Marie‐Jo , Hilly Mauricette , Mauger Jean‐Pierre , Marty Isabelle , De Waard Michel , Villaz Michel , Albrieux Mireille 
Published: March 2003

AbstractThe developmental changes of intracellular calcium release channels of mouse neocortex were studied at the onset of neurogenesis, which occurs between embryonic days E11 and E17. The three main isoforms of the two families of intracellular calcium release channels, namely the inositol trisphosphate receptors (IP3R) and the ryanodine receptors (RyR), were detected by their transcripts in the cerebral hemispheres, as early as stage E11. The major isoforms of each family, IP3R‐1 and RyR‐2, were found at the protein level by Western blot analysis. Expression of these proteins increases progressively throughout brain development. Their localization in coronal sections of cortex has been observed by immunodetection from E12, and compared to the TuJ1 (anti‐class III β‐tubulin antibody) neuronal specific labelling. The expression of both channels is greatly enhanced after E12, and both were seen to be present in most of the proliferative and neuronal cells of the slice. Between E12 and E13, there is a striking transition in the pattern of calcium release elicited by specific agonists of these channels, thimerosal for IP3R and caffeine for RyR. The signals induced by thimerosal were not zone‐specific, while the observed calcium release signals induced by caffeine were predominantly restricted out of the ventricular zone. This zone‐specific caffeine sensitivity is consistent with the main RyR localization immunodetected at E13. Our results indicate that there is a time lag of several days between the molecular detection of calcium release channels and their functional expression, around the time of neuronal differentiation. Altogether, they provide a molecular basis for analyzing the developmental modulation of calcium signals useful for neurogenesis progression.
Nerve growth factor in combination with second messenger analogues causes neuronal differentiation of PC12 cells expressing a dominant inhibitory Ras protein without inducing activation of extracellular signal‐regulated kinases
Authors: Boglári Gábor , Szeberényi József 
Published: March 2003

AbstractIn the present work, nerve growth factor (NGF) was used in combination with the calcium ionophore, ionomycin or dibutyryl cyclic AMP (dbcAMP), to study the connection between neuronal differentiation and extracellular signal‐regulated kinase (ERK) activation of PC12 rat pheochromocytoma cells expressing a dominant negative, Ha‐Ras Asn17 protein. Due to the block of endogenous Ras activity, neurite outgrowth in response to NGF is completely inhibited in these cells. However, this blockade can be bypassed by combined treatment with NGF plus ionomycin or NGF plus dbcAMP. The mitogen‐activated protein kinase (MAPK)/ERK kinase inhibitor, PD98059, proved to be insufficient in inhibiting the neurite outgrowth under these conditions. Moreover, although both long‐term ERK activation and nuclear translocation of ERKs are believed to be key events in neuronal differentiation, neither detectable ERK phosphorylation, nor nuclear translocation of these enzymes, occurred upon combination treatments in our experimental system. However, the neuritogenesis induced by either the combination of NGF/ionomycin or NGF/dbcAMP was inhibited by the Trk inhibitor, K252a. Ras‐independent pathways, originating from the NGF receptor, can thus synergize with second messenger analogues bypassing the ERK cascade but leading to the same biological result – neurite formation.