bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cocaine self‐administration increases the incentive motivational properties of the drug in rats
Authors: Deroche Véronique , Le Moal Michel , Piazza Pier Vincenzo 
Published: March 2003

AbstractA progressive increase in the frequency and intensity of drug use is one of the major behavioural phenomena characterizing the development of addiction. The nature of the drug‐induced adaptations involved in this escalating drug intake remains unknown. Some theories propose that this escalation is due to a progressive decrease (tolerance) in the reinforcing or incentive effects of the drug. Alternative views posit that with chronic use the reinforcing or incentive effects of drugs increase, by a sensitization or a learning mechanism. In this report, we address the question of whether escalating cocaine intake is paralleled by an increase or a decrease in the reinforcing and incentive effects of the drug. Using the experimental model of intravenous drug self‐administration with a within‐session dose–response paradigm, we first studied the course of cocaine intake over 14 sessions in rats. After acquisition of cocaine self‐administration, cocaine intake progressively increased at each dose tested. Then rats, previously allowed to self‐administer cocaine during either six or 29 sessions, were compared in three different tests of the incentive and reinforcing effects of cocaine: cocaine‐induced reinstatement of self‐administration, cocaine‐induced runway and cocaine‐induced place conditioning. As compared with rats briefly exposed to cocaine self‐administration (six sessions), rats with the longer experience (29 sessions) exhibited a higher intake of cocaine paralleled by a higher responsiveness in the cocaine‐induced reinstatement and runway tests. Both groups of rats were similarly sensitive to the rewarding effects of the drug as evaluated by the threshold dose of cocaine inducing place conditioning. Our results demonstrate that escalating cocaine intake is paralleled by an increase in the motivational properties of the drug in the absence of apparent signs of tolerance to the reinforcing or incentive effects of cocaine.
Astrocytes are required for the oscillatory activity in cultured hippocampal neurons
Authors: Verderio Claudia , Bacci Alberto , Coco Silvia , Pravettoni Elena , Fumagalli Guido , Matteoli Michela 
Published: March 2003

AbstractSynchronous oscillations of intracellular calcium concentration ([Ca2+]i) and of membrane potential occurred in a limited population of glutamatergic hippocampal neurons grown in primary cultures. The oscillatory activity occurred in synaptically connected cells only when they were in the presence of astrocytes. Microcultures containing only one or a few neurons also displayed oscillatory activity, provided that glial cells participated in the network. The glutamate‐transporter inhibitors L‐trans‐pyrrolidine‐2,4‐dicarboxylic acid (PDC) and dihydrokainate, which produce an accumulation of glutamate in the synaptic microenvironment, impaired the oscillatory activity. Moreover, in neurons not spontaneously oscillating, though in the presence of astrocytes, oscillations were induced by exogenous l‐glutamate, but not by the stereoisomer d‐glutamate, which is not taken up by glutamate transporters. These data demonstrate that astrocytes are essential for neuronal oscillatory activity and provide evidence that removal of glutamate from the synaptic environment is one of the major mechanisms by which glial cells allow the repetitive excitation of the postsynaptic cell.
Accumulation of murine amyloidβ42 in a gene‐dosage‐dependent manner in PS1 ‘knock‐in’ mice
Authors: Nakano Yuka , Kondoh Gen , Kudo Takashi , Imaizumi Kazunori , Kato Masaya , Miyazaki Jun‐ichi , Tohyama Masaya , Takeda Junji , Takeda Masatoshi 
Published: March 2003

AbstractThe establishment of an animal model with a missense mutation of presenilin‐1 (PS1) is an initial step toward understanding the molecular pathogenesis of familial Alzheimer’s disease (FAD) and developing therapeutic strategies for the disease. We previously described a Japanese family with FAD caused by the I213T mutation of PS1, in which typical signs and symptoms of Alzheimer’s disease were observed at the age of 45 ± 4.2 years [Hardy, J. (1997) Trends. Neurosci., 20, 154–159; Kamino, K et al. (1996) Neurosci. Lett., 208, 195–198]. Here, we report the establishment of ‘knock‐in’ mice with the I213T PS1 missense mutation. Northern blot and reverse transcription polymerase chain reaction (RT‐PCR) analyses showed that the mutated PS1 allele was expressed at the same level as the endogenous PS1 allele, demonstrating that the PS1 missense mutation was successfully introduced into the mouse PS1 locus, and therefore that the situation mimics that in FAD patients bearing PS1 missense mutations. Amyloid beta (Aβ) 42(43) peptide, but not Aβ40 peptide, accumulated in ‘knock‐in’ mice at the age of 16–20 weeks. A clear gene‐dosage effect on the increase of Aβ42(43) was observed in ‘knock‐in’ mice: the percentage increase of Aβ42(43) in mice with mutations in both alleles was twice as high as that in mice with a single allele. These results indicate that the level of the mutated PS1 gene expression is likely to be critically involved in the production of highly amyloidogenic Aβ42(43), and confirm that PS1 mutation has an important effect on amyloid precursor protein (APP) processing, in proportion to the level of the expression of the mutant gene.
Ectopic expression of the bHLH gene Math1 disturbs neural development
Authors: Isaka Fumiaki , Ishibashi Makoto , Taki Waro , Hashimoto Nobuo , Nakanishi Shigetada , Kageyama Ryoichiro 
Published: March 2003

AbstractThe basic helix–loop–helix gene Math1, a positive regulator of neuronal differentiation, is specifically expressed in the dorsal part of the developing nervous system. To determine the effects of ectopic expression of Math1, we generated two transgenic mouse lines; One carried the Cre recombinase gene under the control of the nestin promoter and enhancer, which direct expression in neural precursor cells, and the other carried the Math1 gene, the expression of which was regulated by the cytomegalovirus (CMV) promoter but interrupted by the stop cassette flanked by loxP sites. In F1 embryos that carried the two transgenes, the stop cassette was removed by Cre recombinase in the developing nervous system, and Math1 expression was ectopically directed from the CMV promoter. We found that these embryos exhibited abnormal morphology of the brain and extensive cell death in the nervous system. These results suggest that ectopic expression of Math1 is toxic to neurons and leads to apoptosis.
Interocular temporal delay sensitivity in the visual cortex of the awake monkey
Authors: Perez Rogelio , Gonzalez Francisco , Justo Maria S. , Ulibarrena Carlos 
Published: March 2003

AbstractDue to the separation of the eyes, temporal retinal disparities are created during binocular stimulation and they have been proposed to be the basis of several stereo‐visual effects. This paper studies the sensitivity of cortical neurons from area V1 to interocular temporal delay in the awake monkey (Macaca mulatta). Forty‐four cells were included in this study. Temporal delay sensitivity was observed in 59% of them. About half of these temporal‐delay‐sensitive cells were also sensitive to the stimulation sequence of the eyes. The cells that preferred one eye to be stimulated first were termed asymmetrical (46%); those which were not sensitive to the eye sequence of stimulation were termed symmetrical (54%). No clear differences were observed in the distribution of delay‐sensitive cells according to their eye dominance. Fifty‐six percent of balanced cells and 65% of unbalanced cells were sensitive to interocular delay. These data underline the importance of temporal cues for depth perception.
Visuospatial attentional functioning in mice: interactions between cholinergic manipulations and genotype
Authors: Humby Trevor , Laird Fiona M. , Davies William , Wilkinson Lawrence S. 
Published: March 2003

AbstractAttentional functioning in mice was assessed in an analogue of the five‐choice serial reaction time task in which the requirement was to detect brief visual stimuli presented across five spatial locations. Two hybrid strains of mice were assessed; F1 C57Bl/6xDBA/2 and C57Bl/6x129sv. Both strains acquired the task to high levels of performance with, in particular, no problems due to premature responding. At performance, systematic manipulation of the task parameters indicated a pattern of effects consistent with the task, taxing aspects of visuospatial attention. There were some differential effects of task manipulations at baseline across strain. However, the pattern of effects suggested these were likely to be the result of effects on factors other than attentional functioning per se, such as behavioural reactivity and inhibition. There was evidence in both strains of specific, centrally mediated effects of scopolamine on attentional functioning, with the C57Bl/6xDBA/2 hybrid showing greater sensitivity to the drug manipulation. Specific effects on discriminative accuracy were observed at doses of 0.02 and 0.2 mg/kg scopolamine. At the 2 mg/kg dose, large reductions in accuracy were associated with large effects on other measures, including omissions and response latencies, suggestive of nonspecific effects on task performance. These data indicate, for the first time, the utility of operant methods in assessing visuospatial attentional functioning in mice. They confirm the importance of cholinergic mechanisms in attentional processes across species, and suggest interactions between cholinergic mechanisms and genotype in the expression of attentional phenotypes.
Acidic calponin immunoreactivity in postnatal rat brain and cultures: subcellular localization in growth cones, under the plasma membrane and along actin and glial filaments
Authors: Plantier Marc , Fattoum Abdellatif , Menn Bénédicte , Ben‐Ari Yehezkel , Der Terrossian and Elisabeth , Represa Alfonso 
Published: March 2003

AbstractAcidic calponin, an F‐actin‐binding protein, is particularly enriched in brain, where calponin protein and mRNA are mainly expressed by neurons. The presence of calponin immunoreactivity in cultured astroglial cells has been reported, but the presence of acidic calponin in astrocytes in vivo appears equivocal. For the present study, we raised a specific polyclonal antibody against the 16‐residue synthetic peptide covering the sequence E311‐Q326 (EYPDEYPREYQYGDDQ) situated at the carboxy‐terminal end of rat acidic calponin, and we investigated the cellular and subcellular localization of the protein in the developing central nervous system. Our results show that acidic calponin is particularly enriched in: (i) growth cones and submembranous fields of maturing cerebellar and cortical cells, where it codistributes with microfilaments and (ii) glial cells in vivo, including radial glia, glia limitans, Bergmann glia and mature astrocytes, and ex vivo, where acidic calponin strongly colocalizes with intermediate glial fibrillary acidic protein (GFAP) and vimentin filaments. Finally, up to four acidic calponin subtypes with different isoelectric point (pI) values were identified by two‐dimensional gel electrophoresis of cerebellar and hippocampal extracts. The more acidic isoforms were developmentally regulated. As only one single mRNA for acidic calponin has been identified, these isoforms must reflect postsynthesis changes probably related to the particular functions of acidic calponin in maturing cells. Although brain acidic calponin's exact role remains uncertain, the present data suggest that it is involved in neuronal and glial plasticity.
Expression of functional α7 nicotinic acetylcholine receptor during mammalian muscle development and denervation
Authors: Fischer Uwe , Reinhardt Sigrid , Albuquerque Edson X. , Maelicke Alfred 
Published: March 2003

AbstractWe have studied, on the transcriptional, protein and functional level, the expression of α7 nicotinic acetylcholine receptors (nAChR) in the course of rat muscle development, denervation and renervation. At foetal day 13, α7 nAChR expression was observed in somites and developing muscles of the back, but not yet in migrating myoblasts. Two days later, concomitant with myoblast aggregation, the α7 isoform began to be expressed in isolated myoblasts, with the highest level of expression in the frontal zone of the migrating wave. On foetal day 18, a time when the myoblasts in the upper hindleg have fused, α7 nAChR expression was most prominent in the outer layer of muscle tissue. The highest level of expression was observed in the first postnatal week, when practically all muscle cells stained positively for α7 protein. During the following weeks, α7 nAChR expression slowly decreased and practically disappeared in adult hindleg muscle. Following chronic denervation of adult Soleus muscle fibres, expression of α7 nAChR returned within 2–4 weeks.Electrophysiological measurements showed that the α7 nAChR of chronically denervated soleus muscle fibres were functional and, in particular, that they could be activated by choline. The presence of the α7 nAChR in developing and denervated muscle suggests a role for this nicotinic receptor in neuronal pathfinding and/or endplate stabilization.
Alternative splicing generates a novel isoform of the rat metabotropic GABABR1 receptor
Authors: Pfaff Torsten , Malitschek Barbara , Kaupmann Klemens , Prézeau Laurent , Pin Jean‐Philippe , Bettler Bernhard , Karschin Andreas 
Published: March 2003

AbstractHere we present a novel isoform of the metabotropic G‐protein‐coupled receptor for γ‐aminobutyric acid (GABA). The isoform, termed GABABR1c (R1c), differs from the recently identified R1a and R1b receptors by an in‐frame insertion of 31 amino acids between the second extracellular loop and the fifth transmembrane region. Analysis of the rat GABABR1 gene demonstrates that the insertion is the result of an alternative splicing event within a 567‐bp intron between exons 16 and 17. In situ hybridization in the rat brain shows a wide distribution of R1c transcripts and an overlap with the R1a and R1b transcripts. The highest mRNA levels are found in cerebellar Purkinje cells, cerebral cortex, thalamus and hippocampal CA1 and CA3 regions. Western blots and immunodetection of recombinant epitope‐tagged receptors as well as [125I]CGP71872 photoaffinity labelling of cell membranes demonstrate that R1c is correctly expressed, although at a lower level than the previously identified isoforms. When coexpressed with the newly characterized GABABR2, R1c functionally couples to G‐protein‐activated Kir3.1/3.2 channels in Xenopus oocytes and to PLC‐activating chimeric Gαqo subunits in HEK‐293 cells with a similar EC50 for agonists. These data suggest that the R1c isoform represents a functional GABABR in the rat brain.
Long‐term effects of prenatal stress and postnatal handling on age‐related glucocorticoid secretion and cognitive performance: a longitudinal study in the rat
Authors: Vallée Monique , Maccari Stefania , Dellu Françoise , Simon Hervé , Le Moal Michel , Mayo Willy 
Published: March 2003

AbstractThere is growing evidence that stress during prenatal and postnatal periods of life can modify adaptive capacities in adulthoods. The hypothalamo–pituitary–adrenal axis may mediate an animal's responses to perinatal stressful events and thus serve as a neurobiological substrate of the behavioural consequences of these early events. However, little is known about the long‐term effects of prenatal stressors throughout the entire life of the animals. The focus of the present study was to examine the long‐term influences of a prenatal and postnatal stress on glucocorticoid secretion and cognitive performance. Prenatal stress of rat dams during the last week of pregnancy and postnatal daily handling of rat pups during the first 3 weeks of life were used as stressors. The long‐term effects of these manipulations were analysed using a longitudinal approach throughout the entire life of the animals, and were repeatedly tested in adulthood (4–7 months), middle age (13–16 months) and in later life (20–24 months). The study demonstrated that prenatal stress and postnatal handling induced opposite effects on both glucocorticoid secretion and cognitive performance. Prenatal stress accelerated the age‐related hypothalamo–pituitary–adrenal axis dysfunctions; indeed, circulating glucocorticoids levels of prenatally stressed middle‐aged animals are similar to old control ones, and also induced cognitive impairments. In contrast, postnatal handling protected from the age‐related neuroendocrine and behavioural alterations. These results show that the altered glucocorticoid secretion induced by early environmental manipulations is primary to the cognitive alterations observed only later in life and could be one cause of age‐related memory deficits.
Expression of potassium channels during postnatal differentiation of rabbit Müller glial cells
Authors: Bringmann A. , Biedermann B. , Reichenbach A. 
Published: March 2003

AbstractThe postnatal maturation of Müller glial cells from immature radial glial cells is accompanied by specific changes in the activity of distinct types of K+ channels, as shown by whole‐cell and cell‐attached records on freshly isolated cells from retinae of young (postnatal days 1–30, P1–P30) and adult rabbits. (i) The density of inwardly rectifying currents, providing the main K+ conductance in adult Müller cells, was very low (0.8 pA/pF) from P1 to P6 but increased rapidly thereafter until a relatively stable level of 11.0 pA/pF was established at P17. (ii) Transient (A‐type) K+ currents were expressed in all immature cells at a high density (9.6 pA/pF). After P12, both the percentage of cells with A‐type currents and the peak amplitudes of the currents (2.8 pA/pF) declined. (iii) Delayed rectifying K+ currents developed slowly until after P30. (iv) The postnatal maturation of radial glial cells was accompanied by a strong decrease in the activity of large‐conductance, Ca2+‐activated K+ channels, the open probability of which (measured at the resting membrane potential) decreased from 0.69 at P2–4 to 0.06 at P13–14. The developmental decrease of the activity of Ca2+‐activated K+ channels is assumed to be mainly caused by alteration of the resting membrane potential which developed from low values (–49 mV) at P1–6 to high adult values (–84 mV) after P13. The activity of each distinct type of K+ channel investigated is differently modulated by developmental regulation. This may reflect different functional requirements of immature and mature Müller cells.
Different types of calcium channels and secretion from bovine chromaffin cells
Authors: Lukyanetz E. A. , Neher E. 
Published: March 2003

AbstractBovine chromaffin cells possess several types of Ca2+ channels, and influx of Ca2+ is known to trigger secretion. However, discrepant information about the relative importance of the individual subtypes in secretion has been reported. We used whole‐cell patch‐clamp measurements in isolated cells in culture combined with fura‐2 microfluorimetry and pharmacological manipulation to determine the dependence of secretion on different types of Ca2+ channels. We stimulated cells with relatively long depolarizing voltage‐clamp pulses in a medium containing 60 mm CaCl2. We found that, within a certain range of pulse parameters, secretion as measured by membrane capacitance changes was mainly determined by the total cumulative charge of Ca2+ inflow and the basal [Ca2+] level preceding a stimulus. Blocking or reducing the contribution of specific types of Ca2+ channels using either 20 μm nifedipine plus 10 μm nimodipine or 1 μmωCTxGVIA (omega‐conotoxin GVIA) or 2 μmωCTxMVIIC (omega‐conotoxin MVIIC) reduced secretion in proportion to Ca2+ charge, irrespective of the toxin used. We conclude that for long‐duration stimuli, which release a large fraction of the readily releasable pool of vesicles, it is not so important through which type of channels Ca2+ enters the cell. Release is determined by the total amount of Ca2+ entering and by the filling state of the readily releasable pool, which depends on basal [Ca2+] before the stimulus. This result does not preclude that other stimulation patterns may lead to responses in which subtype specificity of Ca2+ channels matters.
A pre‐ and postsynaptic modulatory action of 5‐HT and the 5‐HT2A, 2C receptor agonist DOB on NMDA‐evoked responses in the rat medial prefrontal cortex
Authors: Arvanov Viktor L. , Liang Xiaofu , Magro Pellegrino , Roberts Roy , Wang Rex Y. 
Published: March 2003

AbstractIntracellular recordings were made from pyramidal neurons in layers V and VI of the rat medial prefrontal cortex in slice preparations to investigate the effect of the serotonin 5‐HT2A,2C receptor agonist (–)‐1‐2,5‐dimethoxy‐4‐bromophenol‐2‐aminopropane (DOB) and 5‐hydroxytryptamine (5‐HT) on N‐methyl‐d‐aspartate (NMDA)‐induced responses. Bath application of either DOB or 5‐HT [in the presence of antagonists to 5‐HT1A, 5‐HT3 and γ‐aminobutytric acid (GABA) receptors] produced a concentration‐dependent biphasic modulation of the NMDA responses. They facilitated and inhibited NMDA responses at low (≤ 1 μm DOB and ≤ 50 μm 5‐HT) and higher concentrations, respectively. Both the facilitating and inhibitory action were blocked by the highly selective 5‐HT2A receptor antagonist r‐(+)‐α‐(2,3‐dimethoxyphenil)‐1‐[4‐fluorophenylethyl]‐4‐piperidinemethanol (M100907) and the 5‐HT2 receptor antagonist ketanserin, thus indicating that both facilitation and inhibition were mediated by the activation of the 5‐HT2A receptor subtype. However, the facilitating, but not inhibitory, action of DOB showed a marked desensitization, suggesting that the facilitation and inhibition of NMDA responses resulted from activation of different 5‐HT2A receptor subtypes and/or signal‐transduction pathways. Indeed, the selective PKC inhibitor chelerythrine and the Ca2+/CaM‐KII inhibitor KN‐93 prevented the facilitating and inhibitory action of DOB, respectively. We have generated several lines of evidence to indicate the following scenario. Low concentrations of DOB, at presynaptic nerve terminals, markedly enhance NMDA‐induced release of excitatory amino acids (EAAs), which then act upon both NMDA and non‐NMDA receptors to elicit inward current. The massive inward current masks the postsynaptic inhibitory action of DOB. At higher concentrations, DOB inhibits the release of EAAs and discloses the postsynaptic inhibitory action.