bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oestrogen‐deficient female aromatase knockout (ArKO) mice exhibit ‘depressive‐like’ symptomatology
Authors: Dalla C. , Antoniou K. , Papadopoulou‐Daifoti Z. , Balthazart J. , Bakker J. 
Published: July 2004

AbstractWe recently found that female aromatase knockout (ArKO) mice that are deficient in oestradiol due to a targeted mutation in the aromatase gene show deficits in sexual behaviour that cannot be corrected by adult treatment with oestrogens. We determined here whether these impairments are associated with changes in general levels of activity, anxiety or ‘depressive‐like’ symptomatology due to chronic oestrogen deficiency. We also compared the neurochemical profile of ArKO and wild‐type (WT) females, as oestrogens have been shown to modulate dopaminergic, serotonergic and noradrenergic brain activities. ArKO females did not differ from WT in spontaneous motor activity, exploration or anxiety. These findings are in line with the absence of major neurochemical alterations in hypothalamus, prefrontal cortex or striatum, which are involved in the expression of these behaviours. By contrast, ArKO females displayed decreased active behaviours, such as struggling and swimming, and increased passive behaviours, such as floating, in repeated sessions of the forced swim test, indicating that these females exhibit ‘depressive‐like’ symptoms. Adult treatment with oestradiol did not reverse the behavioural deficits observed in the forced swim test, suggesting that they may be due to the absence of oestradiol during development. Accordingly, an increased serotonergic activity was observed in the hippocampus of ArKO females compared with WT, which was also not reversed by adult oestradiol treatment. The possible organizational role of oestradiol on the hippocampal serotonergic system and the ‘depressive‐like’ profile of ArKO females provide new insights into the pathophysiology of depression and the increased vulnerability of women to depression.
Sympathetic activation triggers endogenous opioid release and analgesia within peripheral inflamed tissue
Authors: Binder Waltraud , Mousa Shaaban A. , Sitte Nicolle , Kaiser Myriam , Stein Christoph , Schäfer Michael 
Published: July 2004

AbstractStress induces analgesia by mechanisms within and outside the brain. Here we show that the sympathetic nervous system is an essential trigger of intrinsic opioid analgesia within peripheral injured tissue. Noradrenaline, injected directly into inflamed hind paws of male Wistar rats, produced dose‐dependent antinociception, reversible by α1‐, α2‐ and β2‐antagonists. α1‐, α2‐ and β2‐adrenergic receptors were demonstrated on β‐endorphin‐containing immune cells and noradrenaline induced adrenergic receptor‐specific release of β‐endorphin from immune cell suspensions. This antinociceptive effect of noradrenaline was reversed by µ‐ and δ‐opioid antagonists as well as by anti‐β‐endorphin. Stress‐induced peripheral analgesia was abolished by chemical sympathectomy and by adrenergic antagonists. These findings indicate that sympathetic neuron‐derived noradrenaline stimulates adrenergic receptors on inflammatory cells to release β‐endorphin, which induces analgesia via activation of peripheral opioid receptors.
Experimental evidence and modeling studies support a synchronizing role for electrical coupling in the cat thalamic reticular neurons in vivo
Authors: Fuentealba Pablo , Crochet Sylvain , Timofeev Igor , Bazhenov Maxim , Sejnowski Terrence J. , Steriade Mircea 
Published: July 2004

AbstractThalamic reticular (RE) neurons are crucially implicated in brain rhythms. Here, we report that RE neurons of adult cats, recorded and stained intracellularly in vivo, displayed spontaneously occurring spikelets, which are characteristic of central neurons that are coupled electrotonically via gap junctions. Spikelets occurred spontaneously during spindles, an oscillation in which RE neurons play a leading role, as well as during interspindle lulls. They were significantly different from excitatory postsynaptic potentials and also distinct from fast prepotentials that are presumably dendritic spikes generated synaptically. Spikelets were strongly reduced by halothane, a blocker of gap junctions. Multi‐site extracellular recordings performed before, during and after administration of halothane demonstrated a role for electrical coupling in the synchronization of spindling activity within the RE nucleus. Finally, computational models of RE neurons predicted that gap junctions between these neurons could mediate the spread of low‐frequency activity at great distances. These experimental and modeling data suggest that electrotonic coupling within the RE nucleus plays an important role in the generation and synchronization of low‐frequency (spindling) activities in the thalamus.
The basolateral complex of the amygdala mediates the modulation of intracranial self‐stimulation threshold by drug‐associated cues
Authors: Hayes Robert J. , Gardner Eliot L. 
Published: July 2004

AbstractLearning and memory appear to be critical aspects of drug abuse; presumably playing an especially important role in craving and relapse. Thus, understanding the interaction of learning‐ and memory‐related brain areas with the classical reward circuitry is of importance. Toward this goal, the effect of drug‐associated contextual cues on intracranial self‐stimulation (ICSS) behaviour was assessed in rats. We used a method that allows the establishment of baseline behaviour, the pairing of drug exposure with unique cues, and testing the effect of cue exposure within the same apparatus. ICSS thresholds were decreased by morphine (5 mg/kg, i.p.) or cocaine (10 mg/kg, i.p.) during five days of paired drug‐cue training sessions. Subsequent presentation of the drug‐associated cues decreased thresholds in the absence of drug. Cues associated with saline had no effect. These results suggest a Pavlovian conditioning phenomenon in which the functioning of brain reward circuitry is modulated by drug‐associated cues. In a second experiment, we tested the hypothesis that the mechanism by which conditioning affects ICSS thresholds may include the basolateral complex of the amygdala (BLC) due to its known role in conditioning and anatomical linkage with classical reward circuitry. Lesions of the BLC abolished the ability of cocaine‐associated cues to lower ICSS threshold. Lesions did not alter response capability or the unconditioned effect of cocaine. We conclude that the BLC is necessary for cues associated with previous drug exposure to modulate activity within or downstream from the classical reward circuitry of the medial forebrain bundle.
Context‐independent directional cue learning by hippocampal place cells
Authors: Chakraborty Subhojit , Anderson Michael I. , Chaudhry Amir M. , Mumford Julie C. , Jeffery Kathryn J. 
Published: July 2004

AbstractIn a symmetrical environment possessing no other polarizing visual cues, the spatially localized firing of hippocampal place cells can be primarily orientated by a reliable distal visual stimulus, such as a white cue card. However, if such a directional cue is made unreliable by being frequently moved in full view of the rat, the rat's internal sense of direction comes, over the course of a few days, to control the orientation of place fields instead. We investigated whether this simple form of ‘cue‐instability’ learning would transfer to a new context, in which the firing patterns of the place cells become reorganized and in which a new spatial representation is thus active. We found that after cue‐instability learning, the ‘remapped’ place field representation in the new environment was also orientated by the internal sense of direction of the rat rather than by the cue card, showing that the cue learning generalized from one context (and hence spatial representation) to another. This contrasts with another kind of place cell learning, in which the cells can acquire the ability to discriminate two spatial locations in one context but do not transfer this discrimination to a new context. We discuss the different effects of context changes on learned place cell activity in terms of the possible architecture of the inputs to place cells.
Phenotypic expression of the targeted null‐mutation in the dopamine transporter gene varies as a function of the genetic background
Authors: Morice Elise , Denis Cécile , Giros Bruno , Nosten‐Bertrand Marika 
Published: July 2004

AbstractThe dopamine transporter (DAT) plays a critical role in calibrating the duration and intensity of dopamine (DA) neurotransmission. Mice in which the DAT gene has been genetically deleted exhibit constitutively high levels of extrasynaptic DA and spontaneous hyperactivity. Numerous studies have characterized the adaptive molecular, physiological, and behavioural consequences of abnormal DA neurotransmission in these mice. In order to determine the genetic background contribution to these phenotypes, the DAT mutation was transferred on C57BL/6JOrl (B6) or DBA/2JOrl (D2) inbred backgrounds for more than ten generations of back‐crossing to derive three B6‐, D2‐, and B6xD2(F1)‐DAT strains. We observed that the genetic background dramatically affects phenotypes previously reported on DAT knockout (KO) mice. Depending on the genetic background, it was possible to restore survival, growth rate and ability to lactate. Interactions with the genetic background were found to modulate both quantitative and qualitative patterns of novelty‐driven spontaneous hyperactivity. The paradoxical calming effect of cocaine was observed for all DAT‐KO mice. However, the genetic background influenced individual threshold responses to both locomotor and rewarding effects of cocaine. These findings reveal the extent of phenotypic variation associated with the DAT mutation. They also provide concrete arguments against the assumption that the normal function of a gene can be inferred directly from its mutant phenotype.
Induction of pseudo‐periodic oscillation in voltage‐gated sodium channel properties is dependent on the duration of prolonged depolarization
Authors: Majumdar Sriparna , Foster Grant , Sikdar Sujit K. 
Published: July 2004

AbstractThe neuronal voltage‐gated sodium channels play a vital role in the action potential waveform shaping and propagation. Here, we report the effects of prolonged depolarization (1–160 s) on the detailed kinetics of activation, fast inactivation and recovery from slow inactivation in the rNav1.2a voltage‐gated sodium channel α‐subunit expressed in Chinese hamster ovary (CHO) cells. Wavelet analysis revealed that the duration and amplitude of a prolonged sustained depolarization altered all the steady state and kinetic parameters of the channel in a pseudo‐oscillatory fashion with time‐variable period and amplitude, often superimposed on a linear trend. The half steady state activation potential showed a reversible depolarizing shift of 5–10 mV with duration of prolonged depolarization, while half steady state inactivation potential showed a hyperpolarizing shift of 43–55 mV. The time periods for most of the parameters relating to activation and fast and slow inactivation, lie close to 28–30 s, suggesting coupling of these kinetic processes through an oscillatory mechanism. Co‐expression of the β1‐subunit affected the time periods of oscillation (close to 22 s for α + β1) in steady state activation parameters. Application of a pulse protocol that mimicked paroxysmal depolarizing shift (PDS), a kind of depolarization seen in epileptic discharges, instead of a sustained depolarization, also caused oscillatory behaviour in the rNav1.2a α‐subunit. This inherent pseudo‐oscillatory mechanism may regulate excitability of the neurons, account for the epileptic discharges and subthreshold membrane potential oscillation and offer a molecular memory mechanism intrinsic to the neurons, independent of synaptic plasticity.
Does amygdaloid corticotropin‐releasing hormone (CRH) mediate anxiety‐like behaviors? Dissociation of anxiogenic effects and CRH release
Authors: Merali Z. , Khan S. , Michaud D. S. , Shippy S. A. , Anisman H. 
Published: July 2004

AbstractThe brain corticotropin‐releasing hormone (CRH) circuits are activated by stressful stimuli, contributing to behavioral and emotional responses. The present study assessed anxiety‐like responses and in vivo neurochemical alterations at the central nucleus of the amygdala (CeA) evoked by exposure to an unfamiliar (anxiogenic) environment. Also, the impact of anxiolytic treatments and those that affect CRH were assessed in this paradigm. Novel environment (new cage) markedly suppressed ingestion of a palatable snack. This effect was dose‐dependently antagonized by diazepam and was utilized as an index of anxiety in the rodent. Although exposure to a novel environment also stimulated the in vivo release of CRH and glutamate at the CeA, various CRH antagonists (e.g. αh‐CRH, Cα‐MeCRH, CP‐154,526, antisauvagine‐30, preproTRH178‐199) did not attenuate the stressor‐elicited behavioral suppression, although Cα‐MeCRH was found to attenuate the freezing response elicited by contextual stimuli that were associated with previously administered footshock. Moreover, central infusion of CRH failed to suppress snack consumption in the home cage. Although diazepam had potent anxiolytic effects in this paradigm, this treatment did not prevent the stressor‐associated release of CRH and glutamate at the CeA. Thus, while neural circuits involving CRH and/or glutamatergic receptors at the CeA may be activated by an unfamiliar environment, the data challenge the view that activation of these receptors is necessary for the expression of anxiety‐like behavioral responses. Rather than provoking anxiety, these systems might serve to draw attention to events or cues of biological significance, including those posing a threat to survival.
Interleukin‐1β modulates state‐dependent discharge activity of preoptic area and basal forebrain neurons: role in sleep regulation
Authors: Alam Md. Noor , McGinty Dennis , Bashir Tariq , Kumar Sunil , Imeri Luca , Opp Mark R. , Szymusiak Ronald 
Published: July 2004

AbstractInterleukin‐1β (IL‐1) is a pro‐inflammatory cytokine that has been implicated in the regulation of nonrapid eye movement (nonREM) sleep. IL‐1, IL‐1 receptors and the IL‐1 receptor antagonist (ra) are present normally in discrete brain regions, including the preoptic area (POA) of the hypothalamus and the adjoining magnocellular basal forebrain (BF). The POA/BF have been implicated in the regulation of sleep–wakefulness. We hypothesized that IL‐1 promotes nonREM sleep, in part by altering the state‐dependent discharge activity of POA/BF neurons. We recorded the sleep–wake discharge profiles of 83 neurons in the lateral POA/BF and assessed the effects of IL‐1, IL‐1ra, and IL‐ra + IL‐1 delivered through a microdialysis probe on state‐dependent neuronal discharge activity. IL‐1 decreased the discharge rate of POA/BF neurons as a group (n = 55) but wake‐related and sleep‐related neurons responded differently. IL‐1 significantly decreased the discharge rate of wake‐related neurons. Of 24 wake‐related neurons studied, 19 (79%) neurons exhibited a greater than 20% change in their discharge in the presence of IL‐1 during waking. IL‐1 suppressed the discharge activity of 18 of 19 responsive neurons. Of 13 sleep‐related neurons studied, IL‐1 increased the discharge activity of five and suppressed the discharge activity of four neurons. IL‐1ra increased the discharge activity of four of nine neurons and significantly attenuated IL‐1‐induced effects on neuronal activity of POA/BF neurons (n = 19). These results suggest that the sleep‐promoting effects of IL‐1 may be mediated, in part, via the suppression of wake‐related neurons and the activation of a subpopulation of sleep‐related neurons in the POA/BF.
Increased expression of Nogo‐A in hippocampal neurons of patients with temporal lobe epilepsy
Authors: Bandtlow Christine E. , Dlaska Margit , Pirker Susanne , Czech Thomas , Baumgartner Christoph , Sperk Günther 
Published: July 2004

AbstractMesial temporal lobe epilepsy (TLE) is associated with pronounced anatomical and biochemical changes in the hippocampal formation including extensive neurodegeneration, reorganization of mossy fibres and sprouting of interneurons. Although the anatomical features and some of the physiological consequences of hippocampal remodeling have been well documented, the molecular mechanisms underlying the profound and orientated outgrowth of hippocampal neurons in TLE are not yet understood. The reticulon protein Nogo‐A has been associated with an inhibitory action on axon growth and plasticity. Using immunohistochemistry and in situ hybridization, we investigated the expression of Nogo‐A in specimens obtained at surgery from patients with TLE compared with those obtained from autopsy controls. In control specimens, Nogo‐A immunoreactivity and mRNA were mainly confined to oligodendrocytes. Only ≈ 40% of the specimens revealed low expression of Nogo‐A mRNA in neurons. In contrast, in TLE patients with and without Ammon's horn sclerosis, Nogo‐A mRNA and immunoreactivity were markedly up‐regulated in most neurons (3.6‐ and 4.4‐fold increases in Nogo‐A mRNA in granule cells of sclerotic and nonsclerotic specimens) and their processes throughout the hippocampal formation. Similar elevations in Nogo‐A mRNA and protein levels were determined by quantitative RT‐PCR and Western blotting. Since Nogo‐A expression was also up‐regulated in specimens without hippocampal sclerosis, it may be induced by seizures prior to progressing neurodegeneration.
Contrasting effects of dopamine and glutamate receptor antagonist injection in the nucleus accumbens suggest a neural mechanism underlying cue‐evoked goal‐directed behavior
Authors: Yun Irene A. , Nicola Saleem M. , Fields Howard L. 
Published: July 2004

AbstractDiscriminative stimuli (DSs) inform animals that reward can be obtained contingent on the performance of a specific behavior. Such stimuli reinstate drug‐seeking behavior, evoke dopamine release in the nucleus accumbens (NAc) and excite and inhibit specific subpopulations of NAc neurons. Here we show in rats that DSs can reinstate food‐seeking behavior. In addition, we compare the effects of injecting dopamine receptor antagonists into the NAc with those of general NAc inactivation on the performance of a DS task. Selective antagonism of D1 receptors reduced responding to the DS and increased the latency to respond, whereas general inactivation of NAc neuronal activity increased the latency to respond to the DS and increased behaviors extraneous to the task, such as responding in the absence of cues and responding on the inactive lever. Based on these results and our previous findings that NAc neuronal responses to DSs are dependent on the ventral tegmental area, we propose a model for the functional role of NAc neurons in controlling behavioral responses to reward‐predictive stimuli.
Amygdala amino acid and monoamine levels in genetically Fast and Slow kindling rat strains during massed amygdala kindling: a microdialysis study
Authors: Shin Rick S. , Anisman Hymie , Merali Zul , McIntyre Dan C. 
Published: July 2004

AbstractWe investigated the neurochemistry of epileptic seizures in rats selectively bred to be seizure‐prone (Fast) vs. seizure‐resistant (Slow) to amygdala kindling. Microdialysis was used to measure levels of amino acids [glutamate, aspartate and gamma‐aminobutyric acid (GABA)] and monoamines (noradrenaline, dopamine and serotonin) during ‘massed’ stimulation (MS) (every 6 min) of the ipsilateral amygdala for a total of 40 stimulation trials. Behavioral seizure profiles together with their afterdischarge thresholds (ADTs) and associated durations were assessed during the procedure, and subsequently were redetermined 1, 7 and 14 days later. Then normal ‘daily’ kindling commenced and continued until the animal reached the fully kindled state. During MS, several generalized seizures were triggered in Fast rats that were associated with long afterdischarge (AD) durations and intermittent periods of elevated thresholds, but in Slow rats, most stimulations were associated with stable ADTs and short ADs. Progressively increasing extracellular glutamate and decreasing GABA was observed in Fast rats during the MS, whereas Slow rats showed levels similar to baseline values. Levels of noradrenaline and dopamine, but not of serotonin, were also increased in both strains throughout the MS treatment. In Fast rats, a dramatic lengthening of AD durations occurred 7 and 14 days following MS, as well as subsequent strong positive transfer to daily kindling, all of which were not seen in Slow rats. Together, these results show that repeated, closely spaced stimulations of the amygdala can differentially alter excitatory and/or inhibitory transmitter levels in a seizure network, and that sensitivity to this manipulation is genetically determined.
Distinct cellular expressions of creatine synthetic enzyme GAMT and creatine kinases uCK‐Mi and CK‐B suggest a novel neuron–glial relationship for brain energy homeostasis
Authors: Tachikawa Masanori , Fukaya Masahiro , Terasaki Tetsuya , Ohtsuki Sumio , Watanabe Masahiko 
Published: July 2004

AbstractThe creatine/phosphocreatine shuttle system, as catalysed reversibly by creatine kinases, is thought to be essential for the storing and buffering of high phosphate‐bound energy in tissues with high energy demand. In the present study, we aimed to clarify the cellular system of creatine biosynthesis and its energy metabolism in the mouse brain by immunohistochemistry for creatine biosynthetic enzyme S‐adenosylmethionine:guanidinoacetate N‐methyltransferase (GAMT), ubiquitous mitochondrial creatine kinase (uCK‐Mi) and brain‐type cytoplasmic creatine kinase (CK‐B). GAMT was expressed highly in oligodendrocytes and olfactory ensheathing glia and moderately in astrocytes, whereas GAMT was very low in neurons and microglia. By contrast, uCK‐Mi was expressed selectively in neurons and localized in their mitochondria in dendrites, cell bodies, axons and terminals. The distinct and almost complementary distribution of GAMT and uCK‐Mi suggests that the creatine in neuronal mitochondria is derived not only from the circulation, but also from local glial cells associated with these neuronal elements. By contrast, CK‐B was selective to astrocytes among glial populations, and was exclusive to inhibitory neurons among neuronal populations. Interestingly, these cells with high CK‐B immunoreactivity are known to be highly resistant to acute energy loss, such as hypoxia and hypoglycemia. Considering that phosphocreatine generates ATP much faster than the processes of glycolysis and oxidative phosphorylation, the highly regulated cellular expressions of creatine biosynthetic and metabolic enzymes suggest that the creatine/phosphocreatine shuttle system plays a role in brain energy homeostasis through a novel neuron–glial relationship.