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  • 1995-1999  (605)
  • 1920-1924
  • 1996  (605)
  • Computational Chemistry and Molecular Modeling  (433)
  • Rat
  • 101
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 112 (1996), S. 58-62 
    ISSN: 1432-1106
    Keywords: H-reflex ; Operant conditioning ; Plasticity ; Spinal cord ; Soleus muscle ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In response to an operant conditioning task, rats can gradually increase or decrease soleus H-reflex amplitude without change in background electromyographic activity or M response amplitude. Both increase (under the HRup mode) and decrease (under the HRdown mode) develop over weeks. The present study investigated reversal of conditioned H-reflex change. Following collection of control data, rats were exposed to one mode (HRup or HRdown) for 50 days, and then exposed to the opposite mode for up to 72 days. Rats responded to each mode exposure with gradual, mode-appropriate change in H-reflex amplitude. This finding is consistent with other evidence that H-reflex conditioning depends on spinal cord plasticity. The effects of exposure to the HRup (or HRdown) mode were not affected by whether exposure followed previous exposure to the HRdown (or HRup) mode. In accord with recent studies suggesting that HRup and HRdown conditioning have different spinal mechanisms, these results suggest that reversal of H-reflex change is due primarily to the superimposition of additional plasticity rather than to decay of the plasticity responsible for the initial change.
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  • 102
    ISSN: 1432-1106
    Keywords: Cell death ; Neurotrophins ; Retrograde labeling ; Tyrosine hydroxylase ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intraparenchymal injections of the neurotoxin 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle in rats destroys the dopaminergic neurons in the pars compacta of the substantia nigra. In other transmitter systems it has been found that axotomy or neurotoxin exposure produces an initial loss of neurotransmitter phenotype, with cell death occurring over a much slower time course. To determine whether this also occurs in dopamine neurons after 6-OHDA, two approaches were utilized. First, the effect of injections of 6-OHDA into the medial forebrain bundle on nigral dopaminergic neurons was studied using combined fluorogold and immunocytochemical labeling. Four weeks after the 6-OHDA injection, there was an 85% reduction in the number of tyrosine hydroxylase (TH)-immunoreactive cells on the lesioned side. In contrast, there was only a 50% reduction in the number of fluorogold-labeled cells on the lesioned side. Second, the time course of the rescue of dopaminergic neurons after 6-OHDA by glial cell line-derived neurotrophic factor (GDNF) was determined using TH immunocytochemistry. Greater numbers of dopamine neurons were rescued 9 weeks after GDNF, compared with counts made 5 weeks after GDNF. Taken together, these results suggest loss of dopaminergic phenotype is greater than cell loss following 6-OHDA injections, and that GDNF restores the phenotype of affected cells.
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  • 103
    ISSN: 1432-1106
    Keywords: Male sexual behavior ; Vasopressin ; Limbic system ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract During sexual behavior in the male rat, peptidergic cells in the medial amygdaloid nucleus become active and release a vasopressin-like peptide. The present experiments were designed to examine hippocampal changes as a result of this peptide's action during sexual behaviors. Chronic field-potential recordings from the hippocampus of male rats were acquired in a wide variety of social and nonsocial circumstances. Hippocampal responses that resemble the known action of the vasopressin-like peptide were seen only with social stimuli such as sexual stimuli and stimuli that led to aggressive behavior between males. The results show that the occasions of peptide action in the hippocampus correlate with the occasions of peptide release as determined by recording from the peptidergic cell bodies. The results are interpreted to indicate that the amygdala projection to the hippocampus has a special role to play in social behavior.
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  • 104
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 112 (1996), S. 24-34 
    ISSN: 1432-1106
    Keywords: Odor sensitivity and selectivity ; Discrimination unit ; Olfactory bulb ; Unit activity ; Olfactometry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Extracellular single-unit responses to odorants with various properties were recorded from mitral/tufted cells over large areas of the olfactory bulb of anesthetized rats. Each cell was exposed to one stimulus set consisting of five different odorants each at five concentrations. The resulting concentration-response profiles were compared. All mitral/tufted cells examined responded to two or more odorants, and the largest proportion of the cells were sensitive to all five odorants. Cells unresponsive to all five odorants regardless of concentration were not observed. Mitral/tufted cells sensitive to all three of the odorants that are known to evoke maximal electro-olfactograms in different regions of the olfactory epithelium were distributed widely throughout the olfactory bulb. There were no significant differences in latencies of odor responses either across recording sites or across odorants. A comparison of the concentration-response profiles suggested that all of the mitral/tufted cells were equally capable of responding to any odorant with their own distinctive pattern, but that the cells tended to show an identical pattern rather than variable pattern of response to different odorants. Five mitral/tufted cells isolated within 800 μm of one electrode track showed different concentration-response profiles. Of 18 simultaneously recorded spike pairs with different amplitudes and discharge patterns recorded incidentally through one electrode at different sites, 10 had different and 8 had identical response patterns to odorants. These results suggest that: (1) mitral/tufted cells are sensitive to a broad spectrum of odorants, but respond with their own patterns to odorants; (2) odor discrimination is not uniform in neighboring cells, and a discrimination unit is comprised of a single cell.
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  • 105
    ISSN: 1432-1106
    Keywords: Neurodegeneration ; Retrograde neuronal cell death ; Perivascular cells ; Fluorogold ; Phagocytosis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thalamic neuronal degeneration after neocortical lesions involve both anterograde and retrograde components. This study deals with the thalamic microglial response after neocortical aspiration lesions, using fluorogold fluorescent prelabeling, to identify retrogradely degenerating thalamocortical neurons, combined with histochemical or immunohistochemical staining of microglial cells. Adult male Wistar rats were injected with the retrograde fluorescent tracer fluorogold, in the right sensorimotor cortex (forepaw area) in order to retrogradely label thalamic neurons projecting to this area. After 1 week, the fluorogold injection site was removed by aspiration, axotomizing at the same time the thalamic projection neurons now retrogradely labeled with fluorogold. After 3, 7, 14, and 28 days the animals were killed and processed for nucleoside diphosphatase histochemistry or complement type 3 receptor immunohistochemistry and class I and II major histocompatibility complex immunohistochemistry using OX42, OX18, and OX6 antibodies. The histological analysis showed a prominent and progressive nucleoside diphosphatase-,OX42-, and OX6-positive microglial cell response in the ventrolateral, posterior, and ventrobasal thalamic nuclei with ongoing retrograde and anterograde neuronal degeneration. Initially the reactive microglia had a bushy morphology and were succeeded by ameboid microglia and microglial cluster cells as the reaction progressed. However, in the reticular thalamic nucleus, which suffered exclusively anterograde neuronal degeneration, a different picture was seen with only bushy microglia. The neurons undergoing retrograde degeneration in the ventrolateral, posterior, and ventrobasal thalamic nuclei were retrogradely labeled by the fluorogold tracer. Individual nucleoside diphosphatase-, OX42-, or OX6-positive microglial cells extended long cytoplasmic processes surrounding fluorogold-labeled neurons and had in some cases apparently phagocytized these. Several microglial cells were thus double-labeled with nucleoside diphosphatase or OX42 and fluorogold. In addition, small nucleoside diphosphatase-positive, fluorogold-labeled perivascular cells were observed in the neocortex near the fluorogold-injected and ablated neocortical areas and in the ipsilateral thalamus. This study demonstrates: (1) that the microglial response to thalamic degeneration after neocortical lesion is graded with a limited reaction to the well-known massive anterograde axonal degeneration and a more extended reaction to the axotomy-induced retrograde cell death; and (2) that also perivascular cells and possibly macrophages may contribute to this reaction, as seen by uptake of fluorogold from axotomized neurons in the degenerating thalamic nuclei.
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  • 106
    ISSN: 1432-1106
    Keywords: Retrorubral field ; Hippocampal formation ; Mesolimbic dopaminergic system ; Phaseolus vulgaris leucoagglutinin ; Tyrosine hydroxylase immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The dopaminergic neurons in the midbrain of the rat are located in three groups: the ventral tegmental area (VTA-A10), substantia nigra (SN-A9), and retrorubral field (RRF-A8). We have recently examined the organization of the projections from the VTA and the SN to the hippocampal formation (HF) in the rat. In the present study we characterize the projections of the RRF to the HF by using anterograde tracing, retrograde tracers, and tyrosine hydroxylase (TH) immunohistochemistry. Following iontophoretical injections of Phaseolous vulgaris leucoagglutinin (PHA-L) into the RRF, anterograde labeling was observed primarily in the ipsilateral subiculum and adjacent CA1 cell field. Sparse labeling was also observed in the CA3 cell field and dentate gyrus. The distribution of RRF neurons projecting to the HF was examined by injecting retrograde fluorescent tracers (fluorogold, fast blue, and nuclear yellow) into several hippocampal areas. The retrograde tracer findings indicate that the medial aspects of the RRF project to the subiculum and adjacent CA1 cell field of both the septal and temporal HF. In order to evaluate the percentage of dopaminergic cells of the RRF projecting to the HF, the retrograde neuronal tracer fluorogold was used in combination with TH immunohistochemistry. The quantitative evaluation of retrograde labeled and TH-immunoreactive (IR) cells showed that RRF projections to the HF are partially (10–18%) dopaminergic. The findings suggest that the general pattern of distribution and organization of the RRF-A8 projections to the HF is similar to that observed in our previous studies examining hippocampal afferents from the VTA and SN. The data also suggest a crude topographical organization of RRF afferents to the HF and a more prominent input to the temporal than to the septal HF.
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  • 107
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    Springer
    Surgical endoscopy and other interventional techniques 10 (1996), S. 490-494 
    ISSN: 1432-2218
    Keywords: Laparoscopy ; Rat ; Tumor take ; Weight loss ; Pneumoperitoneum ; Bowel resection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The ability of laparoscopic techniques to treat malignant disease is controversial. We developed a rat model to assess metabolic and oncological effects of laparoscopic surgery. Methods: Experiment I. The postoperative body weight in 10 rats having laparoscopic bowel resection (group I), 10 rats having open bowel resection (group II) and 5 rats having anesthesia only (group III) was determined. Experiment II. Tumor take was scored in 11 rats having laparoscopic bowel resection (group IV), 11 rats having open bowel resection (group V), 6 rats having CO2 pneumoperitoneum without bowel resection (group VI) and 6 rats having anesthesia only (group VII). All rats had CC531 cancer cells injected intraperitoneally postoperatively. Results: Experiment I. Body weight loss in group I compared to group II (p〈0.036). Rats of group III lost no weight postoperatively. Experiment II. Tumor take was less in the subcutis (p=0.005), parietal peritoenum (p〈0.001) and bowel anastomosis (p=0.021) in group IV compared to group V. Tumor take was significantly greater at all sites except for subcutis in group VI compared to VII (all p〈0.022). Conclusions: Laparoscopic surgery is associated with less postoperative weight loss and less tumor take compared to open surgery. CO2 insufflation appears to increase tumor take.
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  • 108
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    Springer
    Psychopharmacology 123 (1996), S. 374-378 
    ISSN: 1432-2072
    Keywords: Clozapine ; Olanzapine ; Rat ; Lapping behavior
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract As a way of further comparing the behavioral effects of clozapine and olanzapine, dose ranges of these drugs were studied in a task emphasizing fine motor detail of rats' tongue movements during lapping behavior. Rats lapped drops of tap water from a force-sensing disk. From this behavior four variables were derived: peakforce of tongue strikes, duration of tongue contact, number of separate tongue contacts in 2 min, and the rhythm of the lapping behavior as quantified by Fourier analysis. Both clozapine (0.5–4.0 mg/kg, IP, 45 min) and olanzapine (0.25–2.0 mg/kg, IP, 45 min) dose dependently reduced all four measures of behavior. With respect to lick rhythm, a behavioral marker which clearly distinguishes haloperidol from clozapine in this behavioral paradigm, olanzapine was about twice as potent as clozapine, with the two drugs having parallel dose-effect functions. Within-session decrements in behavior previously reported for haloperidol in the lick task were not produced by clozapine nor by olanzapine. Taken together, these data strengthen the idea that the behavioral effects of clozapine and olanzapine are strikingly similar, and thereby emphasize the potential of olanzapine as an atypical antipsychotic agent.
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  • 109
    ISSN: 1432-2072
    Keywords: 7-OH-DPAT ; Apomorphine ; Dopamine ; D3 receptors ; Locomotor activity ; Progressive-ratio ; Quinpirole ; Rat ; Self-stimulation ; Stereotypies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study assessed the effects of IP injections of (±) 7-hydroxy-2(N,N-di-n-propylamino)tetralin (7-OH-DPAT), a dopamine agonist that has been reported to have preferential affinity for the dopamine D3 subtype of receptor, on four behavioural procedures in the rat: 1) spontaneous locomotion, 2) electrical self-stimulation of the ventral tegmental area (VTA), using the curve-shift procedure 3) operant responding for food under a progressive-ratio (PR) schedule and 4) induction of stereotypies. The effects of (±) 7-OH-DPAT were compared to the effects of apomorphine, a non-specific DA agonist, and quinpirole, a selective D2/D3 agonist. All three dopamine agonists decreased locomotor activity at low doses (0.01–0.3 mg/kg), and only apomorphine had clear locomotor stimulant effects at the highest dose tested (3 mg/kg). The three drugs dose-dependently depressed VTA self-stimulation in a similar way, with low doses inducing a fairly parallel rightward shift of the frequency/rate curves and higher doses flattening the curves. In contrast, responding for food under the PR schedule appeared to be differentially affected by the three agonists: 7-OH-DPAT induced a biphasic effect, with a maximal decrease in lever-pressing at 0.1 mg/kg, followed by a return to baseline levels with increasing doses (0.3–3 mg/kg); quinpirole showed a tendency to decrease responding over the whole dose-range tested with a maximal effect of about 50% of baseline between 0.25 and 1 mg/kg, and apomorphine dose-dependently decreased responding, with rats ceasing to respond at 0.3 mg/kg. All three DA agonists induced stereotypies, but there was a difference in the maximal stereotypy score induced by each of the ligands: 7-OH-DPAT produced a lower maximal effect than quinpirole or apomorphine. This indicates that each of the three dopamine agonists preferentially induced different types of stereotypies. Together, these data suggest that the putative dopamine D3 agonist 7-OH-DPAT, at low doses, has depressant effects similar to those induced by low doses of the other two DA agonists. Differences in the behavioural effects of higher doses were, however, mostly observed in two procedures, PR responding and induction of stereotypies.
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  • 110
    ISSN: 1432-2072
    Keywords: Environmental conditioning ; Nicotine ; Rat ; Sensitization ; Behavioral and neurochemical analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have investigated the effects of environmental conditioning on the induction of nicotine sensitization of locomotion, stereotypy and nucleus accumbens dopamine release. Sprague-Dawley rats, some of which had been previously implanted with a microdialysis guide cannula over the nucleus accumbens, were sensitized with 5 days of repeated nicotine (0.6 mg/kg per day, SC) or saline injections (1 ml/kg per day). During nicotine treatment the drug administration was either paired with the microdialysis/activity monitor testing chamber (conditioned) (n=6) or with the animal's home cage (unconditioned) (n=6) and after 60 min the animal was returned to home cage and received a second injection of saline 15 min later. A third group received saline in the testing apparatus followed by nicotine in the home cage (pseudo-conditioned) (n=6). In the guide cannulated animals, 2 mm microdialysis probes were inserted after completing day 5 of treatment and all animals were tested for their response to nicotine (0.6 mg/kg, SC) on day 6. Both locomotor activity and nucleus accumbens dopamine release showed a larger response subsequent to nicotine challenge in the nicotine versus saline pretreated animals in the conditioned group, but not in the unconditioned group. In the pseudo-conditioned group there was an increase in the stereotypy responses to nicotine, however the locomotor and dopamine release responses were not significantly enhanced. The results from the conditioned group were confirmed in animals which were tested for behavioral activation and dopamine release simultaneously (n=5). These findings indicate that nicotine sensitization of locomotor activity and nucleus accumbens dopamine release (using a 5-day pretreatment protocol) is dependent on conditioning the animal to the testing environment during nicotine pretreatment.
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  • 111
    ISSN: 1432-2072
    Keywords: Thyrotrophin-releasing hormone ; RX77368 ; Alzheimer's disease ; AMPA ; Septal-hippocampal ; Working memory ; Delayed non-matching to position (DNMTP) ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the present study was to determine the effect of a thyrotrophin-releasing hormone (TRH) analogue, RX77368, on performance of a working memory test, using a delayed non-matching to position (DNMTP) procedure, in (RS)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced septal-hippocampal lesioned rats. Following a postsurgery recovery period, pretrained rats were tested once daily on DNMTP, 30 min post-administration of RX77368 (1.0 mg kg−1, IP) or saline. AMPA-induced lesions significantly reduced percent correct responses during the second week of testing. Comparison of percent correct responses between days 1 and 13 of testing showed that sham rats significantly improved DNMTP performance, whereas lesioned rats did not. RX77368 significantly reduced general locomotor activity in sham rats in activity boxes, but did not disrupt non-mnemonic measures, such as locomotion and motivation, in the DNMTP test. RX77368 increased percent correct responses in AMPA-lesioned rats on days 8–10 and 11–13. There was also a significant improvement in percent correct responses achieved between day 1 and 13 in RX77368-treated lesioned and sham rats. These results showed that: (i) septal-hippocampal lesioned rats did not improve over the testing period; and (ii) on test days when a significant impairment was present, RX77368 partially improved DNMTP performance.
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  • 112
    ISSN: 1432-2072
    Keywords: Key words Opioids ; Tolerance ; Neurotensin ; NMDA ; Conditioning ; MK-801 ; Morphine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Opiate tolerance involves both associative and non-associative changes. However, procedures designed to distinguish between these two processes have rarely been employed when investigating the physiological basis of such plasticity. The present experiments assessed some of the mechanisms contributing to both associative and non-associative decreases in morphine analgesic potency following repeated IV morphine administration (4 days, 5 mg/kg per day). For one group of rats, testing for morphine analgesia (tailflick) occurred in a context that had been repeatedly paired with morphine administration. Another group of rats, exposed equally to the testing context, handling procedures and morphine, was tested for morphine analgesia in a context that was specifically unpaired with prior drug. Although both of these groups showed a decrease in the drug effect following repeated administrations, those rats tested in the morphine-associated context were significantly more tolerant than the unpaired group. We evaluated the spinal cord involvement of NMDA receptors, as well as the peptide neurotensin in these two types of tolerance. NMDA receptors appeared to mediate non-associative changes in drug potency, as rats tested in either context were less tolerant when morphine administration was preceded with the non-competitive NMDA antagonist, MK-801 (2.5 and 5 nmol). Spinal neurotensin antagonism with [d-Trp11]neurotensin (3 pmol) selectively abolished associative tolerance. These findings provide information about the mechanisms of opiate tolerance and support the distinction between associative and non-associative processes underlying these changes.
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  • 113
    ISSN: 1432-2072
    Keywords: Social recognition ; Memory ; Rat ; Mouse ; Cannabimimetic ; Cannabinoid antagonist ; SR 141716 ; Ageing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Social short-term memory in rodents is based on the recognition of a juvenile by an adult conspecific when the juvenile is presented on two successive occasions. Cannabimimetics are claimed to induce memory deficits in both humans and animals. In the brain, they mainly bind to CB1 receptors for which anandamide is a purported endogenous ligand. SR 141716, a specific antagonist of CB1 receptors, dose-dependently reverses biochemical and pharmacological effects of cannabimimetics. More particularly, it antagonizes the inhibition of hippocampal long-term potentiation induced by WIN 55,212-2 and anandamide, and it increases arousal when given alone. The present experiments study the ability of SR 141716 (from 0.03 to 3 mg/kg SC) to facilitate short-term olfactory memory in the social recognition test in rodents. SR 141716 improved social recognition in a long intertrial paradigm with a threshold dose of 0.1 mg/kg SC. At 1 mg/kg, it antagonized the memory disturbance elicited by retroactive inhibition. Scopolamine (0.06 mg/kg IP) partially reversed its memory-enhancing effect. Moreover, SR 141716 reduced memory deficit in aged rats (0.03–0.1 mg/kg) and mice (0.3–1 mg/kg). As SR 141716 is not known to exhibit any pharmacological activity which is not mediated by CB1 receptors, the results strongly support the concept that blockade of CB1 receptors plays an important role in consolidation of short-term memory in rodents and suggest there may be a role for an endogenous cannabinoid agonist tone (anandaminergic) in forgetting.
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  • 114
    ISSN: 1432-2072
    Keywords: SKF 38393 ; Quinpirole ; SCH 23390 ; l-Sulpiride ; Nucleus accumbens shell ; Nucleus accumbens core ; Turning behaviour ; Dopamine D1 and D2 receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The goal of this study was to determine whether dopamine D2 and/or D1 receptors in the shell and the core of the nucleus accumbens of rats have a differential role in turning behaviour. Unilateral injection of a mixture of the dopamine D2 receptor agonist quinpirole (10 µg) and the dopamine D1 receptor agonist 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7, 8-diol (SKF 38393, 5 µg) into the shell of the nucleus accumbens produced contralateral turning, when doses which per se were ineffective were injected. This effect was far greater than that found after similar injections into the core of the nucleus accumbens. The effect elicited from the shell was significantly attenuated by prior administration of either the dopamine D2 receptor antagonistl-sulpiride (25 ng/0.5 µl) or the dopamine D1 receptor antagonist (8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol (SCH 23390, 0.5 µg/0.5 µl) into the same region. These data together with the fact thatl-sulpiride is known to be a valid tool to differentiate the involvement of distinct regions within the shell underlie the conclusion that dopamine D2 and D1 receptors in the shell, but not the core, of the nucleus accumbens play a critical role in the contralateral turning induced by unilateral injection of dopamine receptor agonists into this nucleus. The results are discussed in view of the known output pathways of the shell.
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  • 115
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    Psychopharmacology 126 (1996), S. 286-292 
    ISSN: 1432-2072
    Keywords: Modafinil ; Ephedrine ; Cocaine ; Amphetamine ; Self-administration ; Drug discrimination ; Rhesus monkey ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Modafinil [(diphenyl-methyl)sulphinyl-2-acetamide] is a novel psychostimulant drug which is effective in the treatment of narcolepsy and idiopathic hypersomnia. It also has neuroprotective effects in animal models of striatal neuropathology. Although the cellular mechanisms of action of modafinil are poorly understood, it has been shown to have a profile of pharmacological effects that differs considerably from that of amphetamine-like stimulants. There is some evidence that modafinil has central α1-adrenergic agonist effects. In the present study modafinil was evaluated for cocaine-like discriminative stimulus effects in rats and for reinforcing effects in rhesus monkeys maintained on intravenous cocaine self-administration. Modafinil,l-ephedrine andd-amphetamine all produced dose dependent increases in cocaine-lever responding, with maximal levels of 67%, 82% and 100%, respectively. Modafinil produced full substitution in four out of the six rats tested while the highest levels of substitution were associated with substantial response rate decreasing effects. Little evidence was obtained that the discriminative stimulus effects of modafinil were produced by α1-adrenergic activation, based upon results of tests performed in combination with prazosin. In the self-administration procedure, modafinil andl-ephedrine functioned as reinforcers in rhesus monkeys. The reinforcing and discriminative stimulus effects of modafinil required very high doses: modafinil was over 200 times less potent thand-amphetamine and was also less potent thanl-ephedrine. These results show that modafinil has some cocaine-like discriminative stimulus effects and, like other abused stimulants, can serve as a reinforcer at high doses.
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  • 116
    ISSN: 1432-2072
    Keywords: 5-HT1B ; 5-HT1D ; Guinea pig ; Rat ; Locomotor activity ; Prepulse inhibition ; Startle ; Serotonin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The serotonin (5-HT) 1B receptor in rats and mice appears to be homologous to the 5-HT1D receptor found in other mammals, such as guinea pigs and humans. The present series of experiments explored the functional similarity between the rat 5-HT1B receptor and the guinea pig 5-HT1D receptor on two behavioral measures known to be influenced by 5-HT1B receptor manipulations in rats: prepulse inhibition of the startle response (PPI) and locomotor activity. Because the 5-HT1B agonist RU 24969 disrupts PPI and stimulates locomotor behavior in rats, it was predicted that the 5-HT1D agonist, SDZ 219–964, would demonstrate a similar behavioral profile in guinea pigs. In support of this hypothesis, SDZ 219–964 was found to disrupt PPI dose-dependently (1.0 and 2.0 mg/kg) without significantly affecting startle amplitude and to increase locomotor activity (0.5–2.0 mg/kg) in guinea pigs. In guinea pigs, RU 24969 failed to affect PPI, although it did increase locomotor activity, indicating that RU 24969 may have activity at the 5-HT1D receptor. As expected, RU 24969 in rats disrupted PPI (2.5 and 5.0 mg/kg) and significantly increased locomotor activity (1.25–5.0 mg/kg). In rats, however, SDZ 219–964 had generalized, stimulatory effects on startle reactivity, without independent effects on PPI or locomotor activity. The spatial patterns of locomotion exhibited by guinea pigs treated with SDZ 219–964 versus those of rats treated with RU 24969 demonstrate important qualitative differences in structure, indicating that the neural substrates subserving these effects may be different. It is concluded that a functional similarity exists between 5-HT1D and 5-HT1B receptors with regard to the modulation of sensorimotor inhibition and, to a lesser extent, locomotor activity.
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  • 117
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    Psychopharmacology 123 (1996), S. 98-102 
    ISSN: 1432-2072
    Keywords: Sucrose ; Raclopride ; 5-HT2 antagonism ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined the effects on sucrose consumption of a dopamine (DA) D2/D3 antagonist (raclopride, 0–0.3 mg/kg), a serotonin 5-HT2/2c antagonist (ritanserin, 0–0.4 mg/kg), and raclopride (0.15 mg/kg) combined with ritanserin (0–0.4 mg/kg). Three different concentrations of sucrose solution (0.7%, 7.0% and 34%) were tested. The concentration-intake function in drug-free rats was an inverted-U, with 7.0% sucrose supporting the highest intake. Raclopride (0.3 mg/kg) inhibited intake of 7.0% sucrose, but its effect on 0.7% sucrose fell short of significance (P〈0.06) and intake of 34% sucrose was unchanged. Ritanserin did not affect sucrose intake when given on its own, but synergized with a previously ineffective dose of raclopride (0.15 mg/kg) so as to cause a significant inhibition of 7.0% sucrose intake and increase in 34% sucrose intake. These data indicate that 5-HT2 antagonism potentiated the behavioural effects of raclopride and we speculate that this interaction might contribute to the efficacy of atypical neuroleptic drugs.
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  • 118
    ISSN: 1432-2072
    Keywords: 2,4-Dithiobiuret ; Rat ; Cognitive facilitation ; Motor impairment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 2,4-Dithiobiuret (DTB) is a sulfonated derivative of urea that is used as a reducing agent in chemical manufacture. Its low acute toxicity to rodents belies a peripherally mediated, delayed-onset muscle weakness which develops during repeated daily exposure. In experiment 1, a standard dose regimen of DTB (0.5 mg/kg per day IP for 5 days) was used to induce motor dysfunction as a way to dissociate peripheral and central influences on a test of cognitive and motor function in rats. Sixteen male rats were trained to perform a Delayed Matching-to-Position/Visual Discrimination (DMTP/VD) task which permits quantification of working memory (matching accuracy), reference memory (discrimination accuracy), and motor function (choice response latency and nosepoke inter-response time, IRT). The first dose of DTB significantly increased matching accuracy; during the following week, DTB reduced matching accuracy, increased choice response latency and nosepoke IRT, and reduced trial completion. Discrimination accuracy remained unaffected. Experiment 2 explored the effects of single administrations of DTB on DMTP/VD. Sixteen other trained rats were divided into two groups with equal matching accuracy. One group received DTB (0.5,1.0, and 2.0 mg/kg, IP) in separate injections at least 1 week apart; the other group received vehicle at the same times. Matching accuracy increased significantly in the treated rats and not in the controls following each dose of DTB. The magnitude of this increase was dose-dependent, and lasted from 1 to 8 weeks after each injection. Discrimination accuracy, response latency, nosepoke IRT and trial completion remained unaffected throughout the study. After DTB, matching accuracy was less easily disrupted by scopolamine (0.1–0.3 mg/kg, IP). However, DTB did not alter the rats' response to reducing the distance between the response levers, to reversal of the matching rule to a nonmatching rule, or to challenge with MK-801 (0.05–0.10 mg/kg, IP). These data indicate that acute DTB causes a long-lasting facilitation of working memory in rats in the absence of any of the indications of motor impairment which follow repeated, daily injections of the chemical.
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  • 119
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    Psychopharmacology 123 (1996), S. 280-288 
    ISSN: 1432-2072
    Keywords: Ventral pallidum ; Self-stimulation ; Dopamine ; Dopamine antagonists ; 7-OH-DPAT ; Cocaine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study examines the role of dopaminergic neurotransmission in modulating the reinforcing effect of ventral pallidum (VP) intracranial self-stimulation (ICSS). Fifty four adult rats were implanted with a monopolar moveable stimulating electrode in the VP. Rate-frequency functions were determined by logarithmically decreasing the number of pulses in a stimulation train from a value that sustained maximal responding to one that did not sustain responding. After the ICSS thresholds stabilized, the animals received treatments with several doses of cocaine and of various selective drugs acting at the level of DA receptor subtypes. Their effects on threshold and asymptotic rate were analyzed. Cocaine produced a significant decrease in ICSS threshold but had no significant effect on the asymptotic rate. A significant decrease in ICSS threshold was also seen with the D3 agonist 7-OH-DPAT. This was associated with a decrease rather than an increase in performance. D1 and D2DA receptor blockers (haloperidol, SCH-23390, raclopride and sulpiride) produced a dose dependent increase in ICSS threshold and a decrease in the maximal rate. The results suggest that DA plays a modulatory role in VP intracranial self-stimulation, and that D1, D2 and D3 receptors are involved in the mediation of this effect, although to different extents.
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  • 120
    ISSN: 1432-2072
    Keywords: Key words Thyrotrophin-releasing hormone ; RX77368 ; Alzheimer’s disease ; AMPA ; Septal-hippocampal ; Working memory ; Delayed non-matching to position (DNMTP) ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the present study was to determine the effect of a thyrotrophin-releasing hormone (TRH) analogue, RX77368, on performance of a working memory test, using a delayed non-matching to position (DNMTP) procedure, in (RS)-α-amino-3-hydroxy- 5-methyl-4-isoxazolepropionic acid (AMPA)-induced septal-hippocampal lesioned rats. Following a post-surgery recovery period, pretrained rats were tested once daily on DNMTP, 30 min post-administration of RX77368 (1.0 mg kg–1, IP) or saline. AMPA-induced lesions significantly reduced percent correct responses during the second week of testing. Comparison of percent correct responses between days 1 and 13 of testing showed that sham rats significantly improved DNMTP performance, whereas lesioned rats did not. RX77368 significantly reduced general locomotor activity in sham rats in activity boxes, but did not disrupt non-mnemonic measures, such as locomotion and motivation, in the DNMTP test. RX77368 increased percent correct responses in AMPA-lesioned rats on days 8–10 and 11–13. There was also a significant improvement in percent correct responses achieved between day 1 and 13 in RX77368-treated lesioned and sham rats. These results showed that: (i) septal-hippocampal lesioned rats did not improve over the testing period; and (ii) on test days when a significant impairment was present, RX77368 partially improved DNMTP performance.
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  • 121
    ISSN: 1432-2072
    Keywords: Benzodiazepines ; BZ-1 (ω 1) receptor ; Anxiety ; Elevated plus-maze ; Risk assessment ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The behavioral effects of a wide range of BZ (ω) receptor ligands, including non-selective full (alprazolam, clorazepate, chlordiazepoxide and diazepam) and partial (bretazenil, imidazenil and Ro 19-8022) agonists, and selective BZ-1 (ω 1) (abecarnil, CL 218,872, CL 284,846 and zolpidem) receptor ligands, were compared in the rat elevated plus-maze test. Behaviors recorded comprised the traditional indices of anxiety as well as a number of ethologically derived measures. In addition, the specificity of drug effects was evaluated by measuring spontaneous locomotor activity in activity cages in separate groups of animals. Results showed that all compounds tested not only increased the proportion of time spent and proportion of entries into the open arms of the maze (considered as traditional indices of anxiety) but also affected headdippings and attempts at entry into open arms, which can be considered as indices of risk assessment responses. However, the magnitude of these effects was generally smaller with the BZ-1 (ω 1) selective agents. Moreover, additional differences were apparent on the total number of arm entries measure, which was significantly increased by most full and all partial agonists, but was unaffected by the selective BZ-1 (ω 1) compounds. If it is assumed that total arm entries are contaminated by anxiety, the latter finding indicates a weaker anxiety-reducing potential of selective BZ-1 (ω 1) ligands. Importantly, the increase in total arm entries induced by the non-selective agents was not associated with a similar effect on locomotion as revealed in the actimeter. Finally, anxiolysis produced by the BZ-1 (ω 1) ligands was invariably observed at doses which reduced locomotor activity, suggesting that the anxiolytic-like effects of these compounds are confounded by decreases in locomotor activity.
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  • 122
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    Psychopharmacology 125 (1996), S. 202-208 
    ISSN: 1432-2072
    Keywords: Self-administration ; Stimulus control ; Incentive-motivation ; Additive summation ; Cocaine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Presenting independently established discriminative stimuli in compound can substantially increase response rates under food and shock-avoidance schedules. To determine whether this effect extends to drug self-administration, rats were trained to press a lever to receive cocaine intravenously. A tone and a light were independently established as discriminative stimuli for cocaine self-administration, then presented in combination in a stimulus-compounding test. Compared to tone and light alone, the tone-plus-light compound stimulus increased responding approximately three-fold when cocaine was withheld during testing, and it increased drug intake approximately two-fold when cocaine was made available during testing. Compounding did not increase responding after training in a truly random control condition where tone and light were presented uncorrelated with the availability of cocaine. The results obtained with this animal model of drug abuse define conditions under which combinations of environmental stimuli might substantially increase human drug use.
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  • 123
    ISSN: 1432-2072
    Keywords: Nicotine ; Lobeline ; Stimulus discrimination task ; Cognition ; Memory ; Cholinergic ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study evaluated the effects of two central nicotinic-cholinergic receptor agonists and an antagonist on performance accuracy of a rat, delayed stimulus discrimination task (DSDT). Rats were trained to discriminate between an auditory and visual stimulus by pressing a right or left lever. To diminish the rat's ability to use mediating spatial strategies to solve the task, computer automated, retractable doors separated the animal from the levers during delay intervals, thus reducing positioning at the lever. After stable baselines were achieved, rats were grouped and administered placebo (saline) and nicotine, lobeline or mecamylamine in a randomized dose series. Each group received two complete series of the selected compound on different occasions. Mecamylamine impaired DSDT accuracy in a dose-dependent manner while optimal doses of nicotine and lobeline significantly improved accuracy. Nicotine differed from lobeline in regard to its interaction with a dose of mecamylamine (1.0 mg/kg) that had not impaired DSDT accuracy. Combined administration of lobeline and mecamylamine was followed by a significantly increased level of DSDT accuracy that was similar to the improvement following administration of lobeline alone. In contrast, combined administration of nicotine and mecamylamine did not result in increased DSDT accuracy. Furthermore, lobeline administration similarly improved accuracy of trials associated with both the light and the tone, while nicotine improved accuracy of trials associated with the light to a much greater degree. These data suggest that the increases in DSDT accuracy associated with lobeline may be expressed through non-nicotinic mechanisms or a nicotinic receptor which is not blocked by mecamylamine.
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  • 124
    ISSN: 1432-2072
    Keywords: Amperozide ; FG5803 ; Haloperidol ; Antipsychotics ; Oral movements ; Chronic administration ; Acute administration ; Acute dystonia ; Tardive dyskinesia ; Extrapyramidal side effects ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Long-term studies of antipsychotic-induced oral movements may serve as a rat model of acute and tardive movement disorders. Vacuous chewing movements (VCM), tongue protrusions (TP), and jaw tremors (TR) were studied in rats during acute and chronic administration of two potential antipsychotics, amperozide and FG5803. Comparisons were made with haloperidol and vehicle. Single intraperitoneal injections of amperozide (0.2, 1, or 5 mg/kg) or FG5803 (1.2, 6, or 30 mg/kg) were without effect on oral behaviors. During long-term drug administration, withdrawal and readministration, endpoint analysis was focused on changes in supranormal oral movements. The maximal mean control frequencies found at 29 sessions during 14 months experiment +2 standard deviations were used to define the upper limit of the normal range. FG5803 (1.2, 6, or 30 mg/kg per day) administered via the drinking water for 12 months, did not produce significant deviations from this normal range with respect to VCM, TP, or TR, and this drug was not studied further. Rats receiving amperozide (0.2, 1, or 5 mg/kg per day) showed dose-related increases in oral movements over the year. The changes began after 3 months of treatment with amperozide 1 and 5 mg/kg per day, but became statistically significant only during the second half of the treatment year. Amperozide 0.2 mg/kg per day did not produce significant changes in oral movements during administration for a year, but drug withdrawal resulted in a significant rise in TP behavior. Haloperidol (1 mg/kg per day) produced increases in supranormal oral movements which tended to level out after 9 months. In all groups with significant elevations (i.e. haloperidol and amperozide 1 and 5 mg/kg per day), there was a persistence of such movements during a month of drug withdrawal. During treatment with amperozide (1 or 5 mg/kg per day), some rats developed a high frequency chewing behavior up to 175 VCMs/min. It is concluded that long-term treatment with amperozide, but not FG5803, produced a tardive pattern of supranormal oral movements. The importance of these findings for the clinical future of amperozide is difficult to predict, due to the unexpected finding of high-frequency chewing, which has not been noticed before during extensive studies of classical neuroleptics.
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  • 125
    ISSN: 1432-2072
    Keywords: Psychostimulant ; Pavlovian conditioning ; Habituation ; Drug state-dependent process ; Conditioned activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Psychostimulant-induced conditioned activity is characterized by the presence of a hyperactivity in drug-free rats exposed to an environment previously paired with the effects of a psychostimulant. According to the habituation hypothesis, conditioned activity arises not through a Pavlovian conditioning process but rather because rats under the effects of the psychostimulant would be unable to habituate normally to the environment paired with these effects. This hypothesis predicts that conditioned activity should not develop in a previously habituated environment. This prediction was tested using a within-subject design. In this design, conditioned activity is evidenced when a group of rats, following a vehicle injection, was more active in a previously amphetamine-paired environment than in a previously vehicle-paired environment. The drug-environment pairing involved administering rats withd-amphetamine (1.25 mg/kg; SC) immediately prior to their placement in one of two distinctive environments. On alternate days, the rats received the vehicle and were placed in the other environment. With this design, it was found that: a) conditioned activity developed in a previously habituated environment; b) its magnitude was independent of the number of amphetamine-environment pairings (two, four or eight pairings); c) this development of conditioned activity did not result from a forgetting of the habituated environment due to a state-dependent retention of the habituation. Taken together, these results do not support the habituation hypothesis of psychostimulant-induced conditioned activity.
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  • 126
    ISSN: 1432-2072
    Keywords: Cannabinoids ; Pigeon ; SR141716A ; Drug discrimination ; Startle ; Fixed consecutive number ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract SR141716A (Sanofi Recherche), a pyrazole derivative with high affinity for rat and human CB1 cannabinoid receptors, has recently been reported to reverse biochemical, physiological and behavioral effects induced by cannabinoid agonists. The present experiments characterized the activity of SR141716A (SR) in behavioral procedures designed to assess its antagonistic and intrinsic effects on unconditioned behavior and on complex learned behaviors. Six adult male pigeons were trained to discriminate injections of 0.56 mg/kg Δ9-tetrahydrocannabinol (Δ9-THC) from vehicle under a two-key, fixed-ratio schedule of food reinforcement. SR (IM) produced a nearly complete blockade of THC-appropriate responding occasioned by the training dose without inducing significant changes in session response rates, but also produced partial substitution for Δ9-THC when administered alone. In another group of pigeons trained under a multiple schedule of signaled and unsignaled fixed consecutive number (FCN) responding, SR had little effect on accuracy, but Δ9-THC produced dose-related decreases in accuracy under both schedule components. SR was also evaluated in acoustic startle procedures in rats. SR produced little effect either on startle amplitude or prepulse inhibition of acoustic startle. In contrast, the potent cannabinomimetic CP-55, 940 produced large decreases in startle responses elicited by 120 dB [A] broad-band noise. These decreases were completely reversed by SR (10 mg/kg, IP). In concurrent measures, SR blocked the hypothermic effect CP-55,940. These results suggest that SR is an effective antagonist of the psychoactive effects of cannabinoids.
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  • 127
    ISSN: 1432-2072
    Keywords: Maternal separation ; Conditioned incentive stimuli ; Conditioned locomotor activity ; Mesolimbic dopamine ; Amphetamine ; Sulpiride ; SCH 23390 ; Clonidine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Adult hooded rats exposed to a repeated maternal separation procedure during the neonatal period showed a blunted expression of locomotor hyperactivity conditioned to the presentation of the daily food ration. We have demonstrated that the expression of food-conditioned anticipatory hyperactivity is sensitive to the response-enhancing effects of systemicd-amphetamine (0.5; 1.0 mg/kg) and to the response-attenuating effects of the selective dopamine D2 antagonist sulpiride (8; 20 mg/kg), the selective dopamine D1 antagonist SCH 23390 (0.01; 0.022 mg/kg) and the mixed α1/α2 adrenoceptor agonist clonidine (5; 15 μg/kg) in a dose dependent manner. Animals from the early separation groups showed a reduced enhancement of activity in response to 0.5 mg/kgd-amphetamine and a greater attenuation of activity in response to 8 mg/kg sulpiride and 5 μg/kg clonidine. Female separated rats also exhibited an attenuated locomotor response to the unconditioned stimulant effects of 0.5 mg/kg systemicd-amphetamine. The experiments confirm that early maternal separation attenuates the response to conditioned appetitive cues in adult rats and implicate altered dopaminergic and noradrenergic function in the changes. It is possible that early maternal separation in the rat may offer a useful preparation for investigation of the neural substrates mediating affective development and affective psychopathology.
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  • 128
    ISSN: 1432-2072
    Keywords: Cocaine ; Dose-response ; Intraperitoneal ; Intravenous ; Repeated administration ; Sensitization ; Locomotion ; Stereotypy ; Conditioned place preference ; Conditioning ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Dose-dependent differences in the rewarding and stimulant properties of cocaine administered intravenously (IV) and intraperitoneally (IP) were compared. Six 2-day conditioning trials were conducted over consecutive days. Rats received cocaine and were placed into a compartment on one day of the trial, and were directly placed into a different compartment without drug on the other day. Rats were exposed to the compartments for either 20 or 40 min. The effects of cocaine on stimulant behaviors, including locomotion and stereotypies, were compared following the first and last injection. After conditioning, three tests were given with 1 rest day intervening each: (1) conditioned place preference (CPP) was measured as an increase in the amount of time animals spent in the injection compartment relative to the noninjection compartment when given access to both, (2) conditioned activity (CA) was measured as an increase in stimulant behaviors in cocaine-treated animals relative to saline controls following an injection of saline in the injection compartment and (3) context-independent sensitization was measured as an increase in stimulant behaviors following an injection of cocaine in the noninjection compartment relative to the animals' behavior following the first injection. Cocaine did not reliably produce sensitization of locomotion under any of the conditions examined. Cocaine produced sensitization of headbobbing that was more robust following IP administration than it was following IV administration. In both cases, sensitization of headbobbing involved a context-independent component. Cocaine produced CPP and CA with both routes of administration. CPP was established more readily with 40-min relative to 20-min exposures following IV administration, whereas CA was more prevalent with 20-min relative to 40-min exposures. This study provides a thorough characterization of the behavioral effects of cocaine administered IV and a new efficient method for assessing the effects of cocaine on conditioned and unconditioned behaviors following repeated administration.
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  • 129
    ISSN: 1432-2072
    Keywords: Alzheimers' disease ; α2-Adrenoceptor antagonists ; Acetylcholinesterase inhibitor ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The cholinergic hypothesis of Alzheimer's disease (AD) has strongly influenced research on learning and memory over the last decade. However, there has been limited success treating AD dementia with cholinomimetics. Furthermore, there are indications that other neurotransmitter systems affected by this disease may be involved in cognitive processes. Animal studies have suggested that norepinephrine and acetylcholine may interact in learning and memory. The current experiments investigate this interaction in a step-down passive avoidance paradigm after coadministration of acetylcholinesterase inhibitors and α2-adrenoceptor antagonists. Administration of acetylcholinesterase inhibitors heptylphysostigmine (0.625–5.0 mg/kg, IP), tacrine (2.5–10.0 mg/kg, PO), velnacrine (0.312–2.5 mg/kg, SC), and galanthamine (0.312–2.5 mg/kg, IP) each enhanced retention of a passive avoidance response at selected moderate doses administered 30–60 min prior to training. The α2-adrenoceptor antagonists idazoxan (0.312–2.5 mg/kg, IP), yohimbine (0.078–0.312 mg/kg, IP) and P86 7480 (0.156–0.625 mg/kg, IP) alone failed to enhance learning in this paradigm. Coadministration of a subthreshold dose of heptylphysostigmine (0.625 mg/kg, IP) with doses of idazoxan, yohimbine or P86 7480 enhanced passive avoidance learning. This synergistic interaction may represent effects of antagonism of presynaptic α2-adrenoceptor since coadministration of heptylphysostigmine and the selective postsynaptic α2-adrenoceptor antagonist SKF104856 did not result in enhanced learning. Taken together these data suggest noradrenergic activation through pre-synaptic α2-adrenoceptor blockade may potentiate cholinergic activity in the formation of a long-term memory trace. These observations may have implications for the treatment of AD with cholinergic and adrenergic agents.
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  • 130
    ISSN: 1432-2072
    Keywords: Dorsal raphe nucleus ; Rat ; WAY-100635 ; 8-OH-DPAT ; Somatodendritic 5-HT1A receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the rat shock-induced ultrasonic vocalization test, the anxiolytic effects of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) obtained after systemic (IP) and intracerebral injection into the dorsal raphe nucleus (DRN) were selectively abolished by pretreatment with the 5-HT1A receptor antagonist WAY-100635 [N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclo-hexanecarboxamide trihydrochloride]. This blockade was demonstrated both after systemic and DRN application of WAY-100635. Therefore, it is concluded that the anxiolytic effects of 8-OH-DPAT are mediated by activation of somatodendritic 5-HT1A receptors.
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  • 131
    ISSN: 1432-2072
    Keywords: d-Fenfluramine ; Metergoline ; 8-OH-DPAT ; WAY-100635 ; Anorexia ; Satiety sequence ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract These studies investigated the involvement of the 5-HT1A receptor in mediatingd-fenfluramine-induced anorexia in the rat. Non-deprived,d-fenfluramine-treated (3.0 mg/kg) rats consumed a reduced amount of a palatable wet mash and showed a temporal advance in the behavioural sequence consistent with satiety. Thus, rats treated withd-fenfluramine ceased feeding and began resting before corresponding controls. Pretreatment with the selective 5-HT1A receptor antagonist WAY-100635 (1.0 mg/kg) had no effect on either the reduced mash consumption or behavioural satiety sequence ofd-fenfluramine-treated animals at a dose which was found to attenuate the anorexia induced by the 5-HT1A receptor agonist 8-OH-DPAT (0.5 mg/kg). Pretreatment with the nonselective 5-HT antagonist metergoline (1.0 mg/kg) attenuated thed-fenfluramine-induced reduction of mash consumption and the advanced offset of feeding. Metergoline pretreatment had no effect on the advanced onset of resting observed ind-fenfluramine-treated animals. These data suggest thatd-fenfluramine reduces food intake, perhaps by enhancing satiety, via a mechanism which does not involve the 5-HT1A receptor subtype. The implications of these results to the utility of the behavioural satiety sequence as a measure of postprandial satiety are discussed.
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  • 132
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    Psychopharmacology 125 (1996), S. 79-88 
    ISSN: 1432-2072
    Keywords: Serotonin ; 8-OH-DPAT ; Feeding ; Instrumental conditioning ; Incentive learning ; Arousal ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract These experiments assessed whether reported increases in food consumption and food-reinforced instrumental performance in undeprived rats by the 5-HT1A agonist 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT) are due to an increment in the incentive value of foods. Against this hypothesis, we found that when undeprived rats were trained to lever press for the food pellets and then allowed to consume the pellets under 8-OH-DPAT, this reexposure decreased subsequent instrumental extinction performance regardless of test drug condition relative to reexposure under vehicle. Although both food consumption and reinforced lever press performance were incremented, 8-OH-DPAT was found generally to reduce instrumental extinction performance and lever pressing during a period when the reinforcer was delivered non-contingently. Rats injected with 8-OH-DPAT were, however, more sensitive to delay of reinforcement, and increased their lever press performance at a 3-s delay but decreased performance at 6-s and 12-s delays relative to animals injected with vehicle. These results are consistent with the hypothesis that 8-OH-DPAT modifies arousal processes in a manner similar to mild stress, thereby acting both to elevate rewarded instrumental performance and to increase sensitivity to the effects of non-reward.
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  • 133
    ISSN: 1432-2072
    Keywords: Antidepressants ; Desipramine ; Fluvoxamine ; Timing ; Fixed-interval peak procedure ; Interval bisection task ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Acute treatment with antidepressant drugs is known to increase the mean interresponse time (IRT) in the IRT 〉72-s schedule of reinforcement. In order to examine the possibility that this effect may reflect an action of the antidepressants on timing processes, we tested the effects of two antidepressants, desipramine and fluvoxamine, on behaviour maintained under two other timing schedules in rats. In the fixed-interval peak procedure (fixed-interval 30-s), acute treatment with desipramine (8 mg kg−1) reduced response rate, whereas acute treatment with fluvoxamine (8 mg kg−1) increased it. Neither drug significantly altered the time to attainment of peak response rate or the Weber fraction. In the interval bisection task (standard durations 2 s and 8 s), the bisection point was not significantly altered by acute treatment with either drug. Chronic treatment with desipramine (8 mg kg−1 b.d.) had no effect on any of the indices of timing under either schedule. Chronic treatment with fluvoxamine (8 mg kg−1 b.d.) reduced the time to attainment of peak response rate but had no effect on the Weber fraction under the fixed-interval peak procedure, and did not alter the bisection point or Weber fraction under the interval bisection procedure. The failure of desipramine and fluvoxamine to increase the time to peak response rate or the bisection point at doses that significantly altered operant response rate suggests that the effect of these drugs on IRT schedule performance is unlikely to reflect an interaction with timing processes.
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  • 134
    ISSN: 1432-2013
    Keywords: Nerve graft ; Magnification ; Motor nerve conduction velocity ; Compound muscle action potential ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Controversy surrounds the value of optic magnification for peripheral nerve surgery. The aim of this study was to compare the loupe magnification with microscope-assisted techniques in a rat tibial nerve graft model. The parameters studied included motor nerve conduction velocity (MNCV), clinical test equivalent (CTE), soleus muscle weight (SMW) and morphometric nerve indices. In the loupe and microscope groups MNCV mean was 26.77 ± 9.37 m/sec and 44.19 ± 11.36 m/sec respectively. MNCV results suggest better regeneration in the microscope group, as confirmed by CTE, SMW and myelinated fibre (MF) diameter.
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  • 135
    ISSN: 1432-2013
    Keywords: Key words Hypobaric hypoxia ; Physical training ; Skeletal muscle ; Muscle fibre type ; Fibre cross-sectional area ; Enzymes of energy metabolism ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Adaptations of skeletal muscle morphology and metabolic enzymes were studied after prolonged training in and exposure to hypobaric (740 –770 mbar) as well as normobaric conditions in rats performing treadmill running training for 10, 21 and 56 days. Animals sacrificed after 91 days served as recovery groups from training and hypobaric exposure for 56 days. The rats were divided into normobaric sedentary (NS) and training (NT) groups and hypobaric sedentary (HS) and training (HT) groups. The weights of extensor digitorum longus (EDL) and soleus (SOL) muscles increased significantly in the 56HS and the 56HT groups compared with the 56NS group, the increase being greatest in the 56HS group. No differences in the mean fibre areas (MFA) of these muscles could be seen, whereas clearly reduced MFAs of type IIA and IIB were observed in the tibialis anterior (TA) muscle. However, fibre area distribution analyses in the EDL and TA muscles showed a higher proportion of larger fibers in the 56HS and 56HT groups than in the respective normobaric groups. On the contrary, in SOL muscles the proportion of smaller fibers was higher in the hypobaric than in normobaric groups at 56 days. Increased activities of citrate synthase and β-hydroxyacyl-CoA-dehydrogenase in SOL and TA muscles in the 56HT group indicate an increase in oxidative capacity. It is concluded that exposure to, and training in moderate hypobaric conditions leads to a positive muscle protein balance which is reflected in increased muscle weights. However, the sites of increased protein synthesis and the possible hyperplasia remain to be studied further.
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  • 136
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    Pflügers Archiv 431 (1996), S. 882-887 
    ISSN: 1432-2013
    Keywords: Key words Contractile ; Staircase ; Calcium ; Rat ; Fast-twitch ; Fatigue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Myosin light chain (P-LC) phosphorylation, which is thought to be the principle mechanism for twitch potentiation in skeletal muscle, is significantly decreased during staircase in fatigued muscle. Attenuated phosphorylation of P-LC could be due to either depressed Ca2+ transients in fatigue, or to some inhibitory influence of contractile activity on myosin light chain kinase (MLCK). Tetanic stimulation, which would presumably result in maximal activation of MLCK, could be used to evaluate these potential mechanisms. P-LC phosphorylation and twitch developed tension (DT) were assessed at 20 and 120 s following a tetanic contraction in either rested or fatigued rat gastrocnemius muscle in situ. P-LC phosphorylation was significantly lower in fatigued muscles (39.7 ± 3.2% vs 54.8 ± 3.5%, 20 s after a 2-s tetanic contraction), while posttetanic potentiation (PTP) was similar in fatigued (189.1 ± 6.5%) versus rested muscle (169.5 ± 2.6%). Tetanic DT was reduced following the fatigue protocol and, thus, the assumption that the MLCK system was fully activated by Ca2+ may not be valid. The potentiation-phosphorylation relationships were linear for both rested and fatigued muscles; however this relationship was shifted markedly leftward in fatigued muscles. It appears that during PTP, equivalent potentiation is attained with correspondingly lower levels of P-LC phosphorylation in fatigued muscle. This enhanced relative potentiation for a given level of phosphorylation could be expected if Ca2+ transients were attenuated in the fatigued muscle. However the results do not rule out the possibility that other factors contribute to potentiation under these circumstances.
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  • 137
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    Pflügers Archiv 433 (1996), S. 166-173 
    ISSN: 1432-2013
    Keywords: Key words Action potential ; Fatigue ; Ischaemia ; Muscle fibres ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The proximal and distal compartments of rat medial gastrocnemius muscle are dominated, respectively by, fast-twitch oxidative and fast twitch glycolytic fibres. In the present study it was hypothesized that repetitive in situ activation with an intact blood supply would cause greater declines in maximal tetanic force, compound action potential (CAP) amplitude and CAP area in the distal compared to the proximal compartment. Furthermore, it was hypothesized that these differences would be eliminated after occlusion of the blood supply to the muscle. A twitch followed by a tetanus (120 Hz, 200 ms duration) was given every 3 s for 2 min. This exercise protocol was applied once with, and once without, blood supply. During the first minute of the exercise, as expected, occlusion enhanced the decline of proximal force to 77.4 ± 0.8%, a level comparable (P〉0.05) to the decline of distal force (79.7 ± 1.2%). In contrast with the hypothesis, CAP amplitude was not significantly affected by occlusion and it changed significantly less in the proximal (to 102.9 ± 4.5%) compared to the distal (to 69.0 ± 6.7%) compartment. During the second minute of activation without blood flow, sudden declines of distal CAP amplitude (to 18.4 ± 3.4%) coupled with parallel declines in force (to 17.6 ± 2.8%) were observed to occur in the distal but not in the proximal compartment. Proximal final force and CAP amplitude were 54.2 ± 2.6% and 80.6 ± 5.9% respectively. Thus, in contrast with the hypothesis, occlusion enhanced the differences between compartments. These results are discussed in relation to fibre type composition and metabolic changes. It is suggested that a loss of force caused by a decreased muscle fibre excitability upon repetitive activation depends not only on fibre type, but also on the intramuscular location of the fibres.
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  • 138
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    Pflügers Archiv 431 (1996), S. 775-785 
    ISSN: 1432-2013
    Keywords: Rat ; Pancreas ; RIN cells ; Gap junctions ; Connexin43 ; Biophysical properties ; Voltage gating
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A communication-deficient cell line (RIN cells, derived from a rat islet tumour), stably transfected with cDNA coding for rat connexin43 (Cx43), was chosen to further assess the mechanism of voltage gating of Cx43 gap junction channels. The experiments were carried out on preformed cell pairs using a dual whole-cell, voltage-clamp method. The junctional current,I j, revealed a time- and voltage-dependent inactivation at transjunctional voltagesV j 〉 ± 40mV When an asymmetrical pulse protocol was used (in cell 1 the holding potential was maintained, in cell 2 it was altered to establish a variableV j), the channels exhibited an asymmetrical gating behaviour:V j,O = −73.7 mV and 65.1 mV for negative and positiveV j, respectively (V j at whichI j is half-maximally inactivated); gj(min) = 0.34 and 0.29 (normalized minimal conductance); τ = 350 ms and 80 ms atV j = 100 mV (time constant ofI j inactivation). Hence, these parameters were more sensitive to positiveV j values. When a symmetrical pulse protocol was used (the holding potentials in cell 1 and cell 2 were altered simultaneously in steps of equal amplitude but of opposite polarity), theV j —dependent asymmetries were absent:V j,O = −60.5 and 59.5; gj (min) = 0.27 and 0.29; τ = 64 ms and 47 ms at 100 mV Putative explanations for these obervations are discussed. A possibility is that the number of channels alters with the polarity ofV j.
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  • 139
    ISSN: 1432-1912
    Keywords: Key words Clozapine ; Haloperidol ; Chronic treatment ; Nucleus accumbens ; Caudate putamen ; Dopamine ; In vivo fast cyclic voltammetry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fast cyclic voltammetry at carbon-fibre microelectrodes was used to investigate the effects of chronic clozapine or haloperidol administration on electrically evoked dopamine efflux in the nucleus accumbens and caudate putamen of the anaesthetized rat. Stimulation trains were delivered to the median forebrain bundle (60 pulses, 350 μs duration) every 5 min, and the evoked dopamine efflux measured as a function of a) the applied stimulus intensity (range 0.2 mA–1.0 mA), and b) the applied stimulus frequency (range 10 Hz–250 Hz). Chronic administration of either clozapine (20 mg/kg × 21 days, p.o.) or haloperidol (1 mg/kg × 21 days, p.o.) significantly reduced electrically evoked dopamine efflux in the nucleus accumbens over the range of stimulus intensities and frequencies tested. The reduction in evoked dopamine efflux observed in the nucleus accumbens of clozapine- and haloperidol-treated rats showed no statistically significant difference. In contrast, only chronic haloperidol treatment significantly reduced evoked dopamine efflux in the caudate putamen. These findings demonstrate that chronic treatment with either the atypical neuroleptic, clozapine, or the typical neuroleptic, haloperidol, produce long-term changes in mesolimbic dopamine function; actions which may underlie their antipsychotic efficacy. They also provide further evidence that the sparing action of clozapine on nigrostriatal dopamine activity may underlie the lower incidence of extrapyramidal side effects associated with its long-term administration.
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  • 140
    ISSN: 1432-1912
    Keywords: Key words Basal ganglia ; Neuropeptides ; Monoamines ; Amino acids ; Microdialysis ; Chromogranin C ; Secretogranin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In vivo microdialysis was used to study the effect of secretogranin II-derived peptides on dynorphin B (Dyn B), dopamine, γ-aminobutyric acid (GABA), glutamate and aspartate release in the substantia nigra and neostriatum of halothane-anaesthesized rats. In the substantia nigra, local infusion of secretoneurin (secretogranin II 154–186) (1–50 μM) increased, in a concentration-dependent manner, extracellular aspartate, glutamate, Dyn B, dopamine and GABA levels. The effect was particularly prominent on aspartate and glutamate levels which, following 50 μM of secretoneurin, were increased by 〉20 and 〉10 fold, respectively. However, the effect of secretoneurin on Dyn B release appeared to be more specific, since a significant increase (〉2 fold) was already observed following 1 μM of secretoneurin. In the neostriatum, Dyn B, glutamate, aspartate and GABA levels were also increased by local secretoneurin infusion, but the effect was less prominent than in the substantia nigra. In the substantia nigra, only Dyn B levels were significantly increased following infusion of 10 μM of the secretoneurin-C terminal (secretoneurin-15C), whereas Dyn B and GABA levels were increased by the same concentration of the secretogranin II C terminus (YM). Only glutamate and aspartate levels were increased by local infusion of 10 μM of secretogranin II 133–151 (LF), a peptide adjacent to secretoneurin in the primary amino acid sequence. In the neostriatum, Dyn B and GABA levels were increased by 10 μM of secretoneurin-15C. Dyn B levels were also increased by 10 μM of YM, and glutamate and aspartate levels were increased by 10 μM of both YM and LF. Thus, secretogranin II-derived peptides affect extracellular levels of several putative neurotransmitter systems monitored in the basal ganglia of the rat with in vivo microdialysis. The effect of Dyn B appears to be specific and related to a physiological role of secretoneurin, since (i) it occurs in an area where secretoneurin-immunocytochemistry has been observed, (ii) is exerted at comparatively low concentrations, and (iii) is mimicked by secretoneurin-15C. The increases in excitatory amino acid levels produced by high concentrations of secretoneurin and other secretogranin II-derived peptides reflect, perhaps, a potential neurotoxicity produced by abnormal accumulation of these peptides.
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  • 141
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    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 736-745 
    ISSN: 1432-1912
    Keywords: Key words NMDA ; Ethanol ; Glycine ; Ca2+ fluxes ; Neurotoxicity ; Cerebellar granule cells ; Cortical cells ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of ethanol and/or glycine on NMDA-induced enhancement of cytoplasmic free Ca2+ concentrations ([Ca2+]i), 45Ca2+ influx, 4-b-[3H]phorbol-12,13-dibutyrate ([3H]PDBu) binding, and neuronal necrosis in cultured rat cortical and cerebellar granule neurons were examined. Using microfluorimetric techniques in combination with rapid perfusion of single brain neurons, we found that glycine (10 μM) was a necessary co-agonist for NMDA-induced depolarization in cerebellar granule cells. In contrast, depolarization with NMDA in cortical cells was observed even without the addition of exogenous glycine as well as in the absence or presence of 1 mM MgCl2. Ethanol (50 mM) inhibited the effects of NMDA in some, but not all, neurons indicative of the existence of ethanol-sensitive and ethanol-insensitive cortical and cerebellar granule neurons. In studies performed in monolayers of cortical and cerebellar granule cells, we observed that the presence of glycine (10 μM) was a necessary prerequisite to unmask inhibitory actions of ethanol on 45Ca2+ influx induced by NMDA. In another set of experiments, we noted that NMDA-induced stimulation of [3H]PDBu binding to monolayers of intact cerebellar granule cells was inhibited by ethanol (50 mM). Finally, we report that ethanol caused a concentration-dependent inhibition of NMDA-induced necrotic cell death, assessed by measuring the ability of cerebellar granule cells to transform 3-[4, 5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) into formazan. In none of the four assays used to demonstrate the inhibitory effects of ethanol on NMDA receptor activity, the ethanol-induced inhibition was reversed by glycine (up to 100 μM). Thus, in contrast to earlier reports, our data suggest that ethanol and glycine produce their effects by acting at different regulatory sites within the NMDA receptor system in brain neurons.
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  • 142
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    Naunyn-Schmiedeberg's archives of pharmacology 353 (1996), S. 168-174 
    ISSN: 1432-1912
    Keywords: Key words Nucleus basalis magnocellularis ; Nicotine ; Physostigmine ; Cortical EEG ; FFT power spectra ; Unrestrained behaviour ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The basal magnocellular nucleus is assumed to play a crucial role in cholinergic activation of the cortical EEG. The aim of this study was to establish whether intraperitoneally applied nicotine may counteract the power asymmetry of the slow waves in the cortical EEG of both hemispheres after an unilateral lesion in the basal nucleus. In 17 rats the basal nucleus (substantia innominata/ventral pallidum) was unilaterally lesioned by ibotenic acid. The lesion produced unilateral power increases of all frequencies up to 20 Hz in the frontal EEG that increased with higher arousal level. Additionally, synchronized spike and wave discharges appeared in the frontal EEG. The results indicate that the basal nucleus suppresses especially the delta EEG waves in the frontal motor cortex during motor active behaviour. Nicotine (0.1 and 1 mg/kg) partially counteracts the power asymmetry of frontal slow waves (2–6 Hz) only during exploratory sniffing but not during grooming and waking immobility. Physostigmine (1 mg/kg) was also effective during exploratory sniffing. The results may indicate a role of nicotinic mechanisms in the information input component of exploratory behaviour.
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  • 143
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    Naunyn-Schmiedeberg's archives of pharmacology 353 (1996), S. 161-167 
    ISSN: 1432-1912
    Keywords: Ageing ; Dihydroxyphenylaceticacid ; Homovanillic acid ; Hypothalamic paraventricular nucleus ; in vivo microdialysis ; Noradrenaline ; Phenylephrine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of age on basal and stimulated noradrenaline release in the hypothalamic paraventricular nucleus (PVN) of the rat was examined by in vivo microdialysis. Microdialysis probes were inserted into the PVN of 3 and 18 month old anaesthetised Sprague Dawley rats and perfused with a modified Ringer solution. Following four basal 30-min collections, transmitter release was stimulated by perfusion with 100 mM potassium for one collection. After re-equilibration, blood pressure was raised 60 mmHg for 30 min by phenylephrine infusion (1–1.3 mg/kg) then a 2-h recovery period followed. Dialysate collections were injected directly onto a reverse phase HPLC-ECD (HPLC with electrochemical detection). Basal extracellular noradrenaline concentrations were found to be similar in adult and old animals. Basal dihydroxyphenylacetic acid (DOPAC) concentrations were significantly greater in old compared to adult rats (P 〈 0.05). Potassium depolarisation induced a significant increase in noradrenaline concentrations in both age groups (P 〈 0.001), however the noradrenaline response to potassium stimulation was significantly reduced in the aged rats (P 〈 0.05). Potassium-induced decreases in DOPAC and homovanillic acid (HVA) concentrations were seen in both age groups. Following phenylephrine infusion, a modest delayed reduction in noradrenaline levels, which failed to reach statistical significance, was seen. Phenylephrine-induced hypertension was associated with decreased DOPAC and HVA concentrations in adult (P 〈 0.05) and old (P 〈 0.05) rats, respectively. These results indicate that ageing is associated with changes in dopaminergic and noradrenergic activity in the PVN of the rat. A reduction in noradrenaline response to maximal stimulation induced by potassium depolarisation was observed with ageing. The alteration in the activity of the catecholaminergic pathways to the PVN induced by phenylephrine infusion appears to be age dependent.
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  • 144
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    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 179-186 
    ISSN: 1432-1912
    Keywords: Adenosine ; Dopamine N-methyl-D-aspartate (NMDA) ; Basal ganglia ; Catalepsy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous work revealed that adenosine antagonists as theophylline reversed neuroleptic-induced catalepsy and potentiated anticataleptic effects of dopamine agonists reflecting specific adenosine-dopamine receptor interactions in the central nervous system. We tested whether similar functional interactions exist between adenosine receptors and glutamate receptors of the N-methyl-D-asparte (NMDA) subtype. The present study demonstrates that the anticataleptic effects of the competitive NMDA receptor antagonist CGP37849 and the non-competitive NMDA receptor antagonist dizocilpine can be potentiated by coadministration of a threshold dose of the adenosine receptor antagonist theophylline (2.5 mg/kg, i.p.) in haloperidol (0.5 mg/kg, i.p.)-pretreated rats. This potentiation was elicited only with higher doses of CGP37849 (4 and 8 mg/kg, i.p.) or dizocilpine (0.16 mg/kg, i.p.) in haloperidol (0.5 mg/kg, i.p.), but not in reserpine (5 mg/kg, i.p.) plus α-methyl-ptyrosine (100 mg/kg, i.p.)-pretreated animals. Therefore, these synergistic interactions seem to be brought about by indirect monoamine-dependent mechanisms rather than direct functional interrelationships between NMDA and adenosine A2a receptors.
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  • 145
    ISSN: 1530-0358
    Keywords: Colostomy ; Colitis ; Permeability ; Colon ; Ussing chambers ; Rat ; Villus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Barrier properties of an isolated colon loop and the remnant colon in continuity with the gastrointestinal tract after colostomy were studied in the rat. METHODS: The in vivo absorption after colonic loop administration of the marker fluorescein sodium was measured as the urinary recovery. The in vitro permeability was measured in Ussing diffusion chambers as the transmucosal passage of [14C]mannitol and of human serum albumin in the isolated and the nonexcluded colonic segments and was compared with the corresponding colonic regions from sham-operated rats at 1 to 14 days after operation. RESULTS: Body weight gain of the rats decreased and diarrhea appeared from day 2 after colostomy. Histologic examination showed mucosal atrophy with decreased villus height in the isolated colonic loop and an increased villus height in the nonexcluded colon segment. Absorption of fluorescein sodium in the isolated loop was increased at 8 and 14 days. Moreover, permeability in the isolated loop was increased for both mannitol and human serum albumin from four days after colostomy compared with the corresponding colonic segments after the sham operation, whereas a decrease in the passage of mannitol was noted in the nonexcluded colon. CONCLUSIONS: Experimentally performed colostomy diversion in the rat induced alterations of the barrier function in both the isolated colonic loop and the nonexcluded colon in continuity with the fecal stream.
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  • 146
    ISSN: 1530-0358
    Keywords: Delayed-type hypersensitivity ; Laparoscopy ; Phytohemagglutinin ; Keyhole limpet hemocyanin ; Laparoscopic-assisted colon resection ; Rat ; Murine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: We evaluated cell-mediated immune function after laparoscopic-assisted and open bowel resection in rats by measuring delayed-type hypersensitivity responses to keyhole limpet hemocyanin (KLH) and phytohemagglutinin (PHA). METHODS: Male Sprague-Dawley rats (n=120) were sensitized to 1 mg of KLH ten days before investigations. Rats were challenged preoperatively, immediately postoperatively, and on postoperative day (POD) 2 with an intradermal injection of 0.3 mg of KLH and 0.2 mg of PHA (at different sites). Averages of two measures of perpendicular diameters (taken 24 and 48 hours postchallenge) were used to calculate the area of induration using the formula for the area of an ellipse, A=(D1/2×D2/2)×π. Anesthesia control animals underwent no procedure (n=40). Open resection group underwent ligation and resection of the cecum (length=2 cm) through a 7 cm midline incision (n=40). In the laparoscopic-assisted resection group, under CO2 pneumoperitoneum (4–6 mmHg), the cecum was identified, dissected free, and exteriorized through a 4 mm port. The cecum was then ligated and resected extracorporeally (n=40). RESULTS: Preoperative responses to both KLH and PHA were the same in all three groups. Furthermore, within each group, postoperative responses were similar. When groups were compared, the anesthesia group responses were significantly greater than the open resection group responses at all time points (P 〈0.05 for all comparisons). Laparoscopic-assisted resection group responses differed from control at only two of eight postoperative measures. Laparoscopic resection group responses were significantly greater than open resection group responses to challenge with both KLH and PHA on POD1 (P 〈0.02, for both comparisons) and POD 4 (P 〈0.05, for both comparisons). CONCLUSIONS: Postoperative cell-mediated immune function is better preserved after laparoscopic-assisted bowel resection than after open resection as assessed by skin antigen testing.
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  • 147
    ISSN: 1438-8359
    Keywords: Cervical sympathectomy ; Stellate ganglion block ; Adrenocorticotropic hormone ; Thyroid-stimulating hormone ; Growth hormone ; Prolactin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To examine the effects of bilateral cervical sympathectomy on the secretion of adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), growth hormone (GH), and prolactin (PRL), 18 male rats were divided into three groups: control (Cont), sham operation (Sham), and bilateral cervical sympathectomy (Symp). All rats were kept under a normal circadian rhythm for 2 weeks. Subsequently, blood was collected and plasma ACTH as well as serum TSH, GH, and PRL levels were measured. The difference in ACTH levels between the Cont and Sham groups was not significant, but ACTH levels in the Symp group were significantly higher than those in the other groups. The difference in TSH levels between the Cont and Sham groups was also not significant, but TSH levels in the Symp group were significantly lower than those in the Cont group. There were no statistically significant differences in GH and PRL levels among these groups. The present results suggest that cervical sympathectomy in the rat increases ACTH secretion and decreases TSH secretion in the pituitary. These effects seem to be due to a mildly increased secretion of melatonin in the pineal body that probably in turn increases corticotropin-releasing factor (CRF) secretion and decreases thyrotropin-releasing hormone (TRH) secretion in the hypothalamus. Extrapolation of these findings to humans suggests that longterm and repeated stellate ganglion block would affect the pituitary secretions of ACTH and TSH.
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  • 148
    ISSN: 1438-8359
    Keywords: Cervical sympathectomy ; Gonadotropin-releasing hormone ; Hypothalamus ; Median eminence ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To examine the effects of cervical sympathectomy on the transport of gonadotropin-releasing hormone (GnRH) between the hypothalamic neurons and the median eminence, 16 male rats were assigned into four groups: control (C), light (L), light-sympathectomy (LS), and light-colchicine (LC). The C group was kept under a normal circadian rhythm for 2 weeks, and the L group was kept under continuous exposure to light for the same period. The LS group underwent bilateral cervical sympathectomy before being kept under continuous light conditions for 2 weeks. The LC group received colchicine into the cerebral ventricle after being kept under continuous light for 12 days; subsequently, this group was also housed for 2 days under continous light. After these procedures, blood was collected and serum luteinizing hormone (LH) levels were measured. All rats were perfused with a fixative, and GnRH neurons around the anterior commissure, as well as GnRH fibers and granules in the median eminence, were stained immunohistochemically. The L group showed a decreased number of GnRH neurons, increased concentrations of GnRH fibers and granules, and an increased LH level; however, in the LS and LC groups, these changes were not seen. The response in the LS group resembled that in the LC group. Considering the action of colchicine, which inhibits axonal transport, it is suggested that cervical sympathectomy also inhibits axonal transports of GnRH between the GnRH neurons and the median eminence during continuous exposure to light.
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  • 149
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    Amino acids 10 (1996), S. 49-57 
    ISSN: 1438-2199
    Keywords: Amino acids ; Taurine ; γ-Aminobutyric acid ; Synaptosome ; Olfactory bulb ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Superfusion of synaptosomes prepared from rat olfactory bulb revealed constant basal release of endogenous taurine (Tau), aspartate (Asp), glutamate (Glu) andγ-aminobutyrate (GABA): their release rates were 110.4 ± 13.0, 30.3 ± 6.7, 93.7 ± 13.1, and 53.3 ± 8.8 pmol/min/mg protein, respectively. The depolarizing-stimulation with 30mM KCl evoked 1.17-, 2.18-, 2.55- and 1.53-fold increases, respectively. Tau release was calcium-independent. However, the perfusion of synaptosomes with Tau (10µM) inhibited the evoked increase in GABA release by 63% without changing basal release, although it did not affect release of Asp and Glu. Phaclofen (10µM, a GABAB receptor antagonist), but not bicuculline (10µM, a GABAA receptor antagonist), counteracted the Tau-induced reduction in GABA release. These data suggest that Tau may be abundantly released from nerve endings of rat olfactory bulb and that it may regulate GABA release through the activation of presynaptic GABAB autoreceptors.
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  • 150
    ISSN: 1534-4681
    Keywords: Regional drug delivery ; Rat ; Immunology ; Testis ; Cancer chemotherapy ; Infertility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Testicular circulatory isolation (TCI), a regional drug exclusion approach designed to prevent chemotherapy-induced male infertility, can reduce testicular drug exposure and preserve fertility. The immunological sequelae of this surgical procedure were investigated. Methods: Forty Sprague-Dawley rats received unilateral TCI for 45 min and were killed at intervals of up to 43 days later. Testicular histology was evaluated qualitatively using hematoxylin and eosin stain, a direct immunofluorescent technique for detection of antigen-antibody complexes, and an indirect immunofluorescent technique to detect circulating antitestis antibodies. Results: No immune-mediated injury was evident up to 43 days after TCI. Conclusion: The current work, taken together with previously published data, indicate that TCI produces no immunological damage in the rat testis. Because TCI is well tolerated in humans, this work also supports the institution of human clinical trials of this technique in men about to receive fertility-threatening chemotherapy.
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  • 151
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    Pflügers Archiv 432 (1996), S. 313-319 
    ISSN: 1432-2013
    Keywords: Key words Soleus muscle ; Rat ; Atrophy ; Unloading ; Motor units ; Contractile properties
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this study was to compare the isometric contractile properties of rat soleus motor units after 14 days of hindlimb unloading (HU) to those under control conditions. The motor units (MU) were classified using two mechanical criteria: the presence or not of a sag during unfused tetani and the value of the twitch time-to-peak (TTP). Under control conditions, the soleus muscle was composed of 85% of slow-type (sag −, TTP 〉 20 ms) and 15% of fast-type (sag +, TTP 〈 20 ms) units. Following HU, these two populations were still present and results showed: (1) large decreases in their maximal tetanic tensions (of −67% and −60% for slow- and fast-type, respectively), and (2) changes in their relative proportions, i.e. a decrease in the percentage of slow-type units and a twofold increase in the percentage of fast-type units were observed. These latter changes might be the consequence of a complete transformation of slow-towards fast-type units. A third population appeared in the HU solei, 26% of the samples, combining the presence of a sag and speed-related properties between those of slow- and fast-type units. These slow-intermediate units might come from slow units partially transformed into a faster type during HU. Thus the present study showed that unloading conditions induced a reorganisation of the soleus motor unit profile. The complete or partial transformation of the motor units could be related to the changes in the electromyographical activity of the unloaded soleus.
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  • 152
    ISSN: 1432-2013
    Keywords: Key words Central chemoreceptors ; Peripheral chemoreceptors ; Fos ; Rat ; Hypercapnia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Exposure to hypercapnia and electrical stimulation of the carotid sinus nerve (CSN) has been shown to induce c-fos expression in several brain stem regions including the nucleus tractus solitarius (NTS). To test whether the labeled neurons were activated directly by hypercapnia or secondarily via the carotid bodies (sinus nerve), adult rats were exposed to either air or 14–16% CO2 for 1 h. Experiments were done on eight groups: (1) exposure to air, (2) exposure to CO2, (3) chronic CSN denervation/CO2, (4) chronic unilateral CSN denervation/CO2, (5) chronic sham CSN denervation/CO2, (6) anesthetized/CO2, (7) anesthetized and acute vagotomy/CO2, and (8) premedicated with morphine, 10 mg s.c., 20 min before exposure to CO2. After exposure to CO2 or air the rats were anesthetized, perfused with 4% paraformaldehyde and the brains processed for immunohistochemical staining for c-fos protein using the PAP (i.e. peroxidase anti-peroxidase) technique. Labeled neurons in the area of the NTS in every second 50-μm section were counted and their position plotted using a microscope and camera lucida attachment. Rats exposed to CO2 had a significantly greater number of labeled neurons in the NTS than those exposed to air. Other interventions, such as CSN denervation, surgery, anesthesia, vagotomy or injection of morphine did not significantly affect the level of c-fos expression in rats exposed to hypercapnia, indicative of central stimulation rather than secondary peripheral input. These responsive neurons may be part of a widespread central chemoreceptive complex.
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  • 153
    ISSN: 1432-2013
    Keywords: Central chemoreceptors ; Peripheral chemoreceptors ; Fos ; Rat ; Hypercapnia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Exposure to hypercapnia and electrical stimulation of the carotid sinus nerve (CSN) has been shown to induce c-fos expression in several brain stem regions including the nucleus tractus solitarius (NTS). To test whether the labeled neurons were activated directly by hypercapnia or secondarily via the carotid bodies (sinus nerve), adult rats were exposed to either air or 14–16% CO2 for 1 h. Experiments were done on eight groups: (1) exposure to air, (2) exposure to CO2, (3) chronic CSN denervation/CO2, (4) chronic unilateral CSN denervation/CO2, (5) chronic sham CSN denervation/CO2, (6) anesthetized/CO2, (7) anesthetized and acute vagotomy/CO2, and (8) premedicated with morphine, 10 mg s.c., 20 min before exposure to CO2. After exposure to CO2 or air the rats were anesthetized, perfused with 4% paraformaldehyde and the brains processed for immunohistochemical staining for c-fos protein using the PAP (i.e. peroxidase anti-peroxidase) technique. Labeled neurons in the area of the NTS in every second 50-μm section were counted and their position plotted using a microscope and camera lucida attachment. Rats exposed to CO2 had a significantly greater number of labeled neurons in the NTS than those exposed to air. Other interventions, such as CSN denervation, surgery, anesthesia, vagotomy or injection of morphine did not significantly affect the level of c-fos expression in rats exposed to hypercapnia, indicative of central stimulation rather than secondary peripheral input. These responsive neurons may be part of a widespread central chemoreceptive complex.
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  • 154
    ISSN: 1434-4726
    Keywords: Endolymph potassium ; Ion-selective microelectrode ; Noise exposure ; Deafness ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Double-barrelled potassium selective microelectrodes (K-ISME) were used in situ for real-time sequential determinations of potassium concentrations (CK+) in endolymph, marginal cells and the spiral ligaments of rats exposed to moderate noise at 100 dB for 30 min (NE) and control (CTL) animals. CK+ in NE animals at these sites did not differ significantly when compared to CK+ in CTL animals. However, there was a slight decrease in CK+ in marginal cells in the noise-exposed animals.
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  • 155
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    European archives of oto-rhino-laryngology and head & neck 253 (1996), S. 214-221 
    ISSN: 1434-4726
    Keywords: Formalin fixation ; Mucous cell ; Submandibular gland ; Morphology ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The features of mucous cells in 10% formalin (FA)-fixed submandibular glands differ markedly from those fixed in glutaraldehyde (GA). We therefore studied morphological changes in mucous cells during 10% FA fixation. Mucous cells were fixed in either 10% FA, neutral sodium-phosphate-buffered (Na-PBed) 10% FA, ice-cold 10% FA or an ice-cold fixative mixture of 2.0% paraformaldehyde (PA) and 0.5% GA. Two different methods were used: immersion fixation and venous perfusion fixation. The 10% FA-fixed tissues had elliptical or flattened nuclei, a clear cytoplasm and no secretory granules. Tissues fixed with the fixative mixture displayed almost round nuclei, a broad endoplasmic reticulum and abundant secretory granules in the cytoplasm. Tissues immersion-fixed with neutral Na-PBed 10% FA or perfusion-fixed with ice-cold 10% FA had almost the same light microscopic appearance as that of the mixture-fixed tissues. To elucidate the process of morphological changes during 10% FA fixation at room temperature, samples immersed in 10% FA for varying periods of time were postfixed immediately in the fixative mixture and exposed to microwave irradiation. This method produced a variety of findings, even within the same section. There was a significant difference in the findings seen in the center of the section and at the periphery. The initial changes caused by 10% FA were rupture of the secretory granules located in the perinuclear region and destruction of the perinuclear organelles such as Golgi apparatus, mitochondria and endoplasmic reticulum. Absorption of the endoplasmic reticulum progressed so that the pennuclear region became translucent. To obtain a better structure in mucous cells from the fixed submandibular gland tissues, an appropriate fixative such as GA should be used and the fixative should infiltrate into the tissue as quickly as possible.
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  • 156
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    European archives of oto-rhino-laryngology and head & neck 253 (1996), S. 142-146 
    ISSN: 1434-4726
    Keywords: Immunocompetent cells ; Mucosal immune system ; Larynx ; Immunohistology ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The larynx can be divided into a supraglottic, a glottic and a subglottic area, each serving different functions. In many cases of laryngitis the site of infection is located in one area, leaving other areas unaffected. It seems reasonable to speculate that the underlying cause of the heterogeneous infection pattern in the larynx is the different processing of infectious agents. Therefore, the number and distribution of granulocytes, macrophages, dendritic cells, natural killer cells and T and B lymphocytes in the normal laryngeal mucosa of young rats were studied. The results show that, with the exception of granulocytes, all subpopulations were present in different numbers. Many macrophages and dendritic cells but only a few natural killer cells and T and B lymphocytes were located in the mucosa. Dendritic cells, natural killer cells and T and B lymphocytes were rarely present in the vocal fold area, whereas in the subglottic area they were present in high numbers. Thus, differences in the composition of immunocompetent cell populations between laryngeal areas were detectable.
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  • 157
    ISSN: 1432-1238
    Keywords: Key words Acute pancreatitis ; Therapy ; Dextran ; Hypertonic ; Colloid ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: Ultrahigh-molecular dextran (500000 Da) has been shown to prevent pancreatic necrosis when given 30 min after induction of pancreatitis. This study should clarify the following: (a) are dextrans still effective after prolongation of the therapy-free interval? (b) what is the impact of the molecular weight of the dextrans? and (c) is their effect influenced by the dextran concentration or by the addition of hypertonic saline? Animals and interventions: Acute pancreatitis was induced in 70 male dextran-tolerant Wistar rats using intraductal bile-salt infusion and intravenous hyperstimulation. After 3 h, animals were assigned to one of seven groups (n=10 per group) receiving either Ringer solution or different dextrans (10%) including 70000 Da (DEX-70), 160000 Da (DEX-160), 300000 Da (DEX-300) or 500000 Da (DEX-500). Additional groups included DEX-70 (6%) and DEX-70 (10%) in combination with hypertonic NaCl (7.5%) (HHS-70). Ringer solution was given at 24 ml/kg and all dextrans at 8 ml/kg. Measurements and results: Trypsinogen activation peptides (TAP) were quantified in ascites and acinar necrosis after death or sacrifice at 9 h. As an index of less pathological trypsinogen activation, the mean TAP levels in ascites were significantly lower in DEX-70 and DEX-160 compared to Ringer controls (p〈0.05, t-test). Furthermore, the amount of acinar necrosis was significantly lower in all dextran groups except the HHS-70 in comparison with Ringer controls (p〈0.01, t-test). Finally, mortality was significantly reduced from 60% in Ringer controls to 10 and 0%, respectively, in the groups treated with DEX-70 and DEX-160 (p〈0.03, Fisher‘s Exact test). There was a similar trend in all other groups except the HHS-70. Conclusions: Despite a therapy-free interval of 3 h, dextrans reduce trypsinogen activation, prevent acinar necrosis, and improve survival in necrotizing rodent pancreatitis. The molecular weight and concentration of dextran are of secondary importance for these beneficial effects.
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  • 158
    ISSN: 1573-0603
    Keywords: Brain ; Histology ; Organotypic culture ; Patch clamp recording ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The goal of the current research was to define an in vitro system that can replace in vivo experimentation but reflects as far as possible aspects of the intact situation of the developing nervous system of mammals. Tissue slices of postnatal rat hippocampi were continuously moved between the medium and gas phase. Under these conditions the complex cytoarchitecture was preserved for many weeks. Lactate dehydrogenase assay, cell size analysis and neuron- and glial cell specific immunocytochemical markers were employed to illuminate explant development in vitro. By scanning electron microscopy the explant surface was analysed in order to determine the conditions suitable for patch clamp recording. Electrophysiological analysis revealed a pronounced spontaneous activity showing the neurons to be functionally active. These data indicate that organotypic roller cultures reflect to a large extent the in vivo situation of the mammalian nervous system. The culture system provides a promising model system for developmental physiology, neurotoxicology and pharmacology.
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  • 159
    ISSN: 1434-0879
    Keywords: Enolase ; Isozymes ; Rat ; Renal neoplasms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Concentrations of enolase isozymes in normal kidney and renal cell tumors in rats were determined using a highly sensitive enzyme immunoassay, and the isozymes were immunohistochemically localized in tissue sections. Levels of α-enolase in renal cell turnors were significantly lower than in normal kidney, whereas those of γ-enolase were significantly elevated (mean ±SD:211±129 ng/mg protein, n=15, as compared to 27.1±2.9 ng/mg protein, n=7). The proportion of γ-enolase in the total enolases in the tumor tissues (1.6±0.5%) was significantly higher than in normal kidney (0.15±0.005). Immunohistochemistry revealed epithelial cells of all nephron segments to be positive for the α-isozyme, whereas γ-enolase staining was strongly positive only in the loops of Henle, being faint in the distal tubules and absent in the proximal tubules. Both α- and γ-enolases demonstrated positive immunostaining in all of the seven renal cell tumors studied. These findings indicate that an isozyme switch from α- to γ-enolase occurs during rat kidney carcinogenesis, taking into account the derivation from proximal tubules, consistent with the findings for renal cell carcinomas in man.
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  • 160
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    International urogynecology journal 7 (1996), S. 30-36 
    ISSN: 1433-3023
    Keywords: Aging ; Incontinence ; Rat ; Smooth ; Sphincter ; Striated ; Urethra
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Muscles in the limbs change with age, but the aging process of urethral muscles is unknown. Therefore, we compared smooth and striated muscle content in the female rat urethra in young (12 month) and old (32 month) animals, using immunochemical techniques. All the striated skeletal fibers at both ages contain slow myosin. Urethral diameter does not change with age (young, 1.44±0.08 mm; old, 1.46±0.10 mm,n=5), nor does the external sphincter width (young, 0.088±0.016 mm; old, 0.080±0.017 mm,n=5). Neither smooth nor skeletal muscle volume in the urethra is changed with age (skeletal: young, 20.72±2.94%; old, 19.95±2.35%. Smooth: young, 22.26±2.98%; old, 26.75±2.35%,n=5). The external striated sphincter is separate and distinct from the pubococcygeal region of the levator ani muscle, but is closely apposed to another layer of longitudinally oriented fibers into the vaginal musculature. The morphometric analysis shows no difference in urethral architecture in aging female rats.
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  • 161
    ISSN: 1615-6102
    Keywords: Aging ; Alzheimer's disease ; Brain ; Cell-free system ; Membranes ; Membrane trafficking ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A cell-free transfer system was used to measure capacity of brain membranes to support membrane renewal. To study transfer in brain, radiolabeled donor microsome fractions were prepared using brain slices from rats or frozen human brain autopsy specimens. Acceptor fractions, prepared from fresh or frozen rat brain or frozen human brain autopsy specimens, were immobilized on nitrocellulose. The complete reconstituted transfer system contained ATP plus ATP-regenerating system (or NADH) as a source of energy and brain cytosol. Slices of frozen brain incorporated acetate into membrane lipids with approximately the same efficiency as fresh brains. This efficiency declined with storage at 4 °C but only slowly. Donor fractions labeled with acetate from frozen slices exhibited specific transfer (37 °C minus 4 °C) of labeled membrane lipids with efficiencies comparable to fresh. The acceptor fraction could be prepared either from fresh or frozen material. Transfer was on the average two-fold stimulated by ATP at 37 °C compared to no ATP. Transfer also was stimulated by NADH. Analysis of linear transfer rates between 0 and 30 min revealed no significant effect of delay time or of time of prolonged storage on transfer efficiency beyond an initial decline of ca. 25% observed within the first two weeks after freezing. A decline of transfer was obtained with brains as the animals aged.
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  • 162
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    European journal of applied physiology 73 (1996), S. 130-135 
    ISSN: 1439-6327
    Keywords: Experimental auto-immune encephalomyelitis ; T-Cells ; Rat ; Auto-immunity ; Exercise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the study was to determine whether different programmes of exercise influence adoptive monophasic experimental auto-immune encephalomyelitis (adoptive EAE), a paralytic disease mediated by T-cells. Adoptive EAE was induced by the transfer of activated encephalitogenic T-lymphocytes into syngeneic recipients (Lewis rats, n = 85) and its development was followed by two independent observers. The results showed that 2 days of severe exercise (250 and 300 min) performed after the adoptive transfer of EAE slightly delayed the onset of the disease (P 〈 0.008) and the day of its maximal severity (P 〈 0.016) without affecting the overall severity of the disease. When this programme of exercise was performed before the cell transfer, it had no effect (P 〉 0.05). Two more moderate exercise programmes (5 × 120 min of running at constant speed or 5 × 60 min of running at variable speed, 5 consecutive days) performed between the adoptive transfer and the onset of the disease did not modify the development of the clinical signs of adoptive EAE (P 〉0.05). These results showed that severe exercise slightly influenced the effector phase of monophasic EAE and confirmed that physical exercise performed before the onset of experimental auto-immune diseases did not exacerbate the clinical signs.
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  • 163
    ISSN: 1619-7089
    Keywords: Pinhole collimator ; Single-photon emission tomography ; High resolution ; Myocardial infarction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this study was to evaluate the accuracy of myocardial imaging by means of high-resolution single-photon emission tomography (SPET) with a pinhole collimator in rats with experimental infarction. Myocardial infarctions were induced in male Wistar rats by ligation of the left coronary artery for 30 min, followed by reperfusion. Two days after the reperfusion, pinhole SPET was performed after the intravenous administration of 111 MBq of thallium-201 chloride, using a rotating gamma camera equipped with a pinhole insert (2.0-mm aperture) in a low-energy pinhole collimator. SPET projection data were collected at 6° increments over 360° using a 4-cm radius of rotation to reconstruct the short- and long-axis images. Projection data were acquired in 15 or 30 s, the SPET imaging being accomplished within 40 min after the injection of201T1. After SPET, the rats were sacrificed to remove the hearts for autoradiography (ARG) and nitroblue tetrazolium (NBT) staining as a visual correlative study. Quantitative correlative studies between pinhole SPET and ARG were performed with linear regression analysis for infarct size and distribution properties (relative counts on SPET images and relative density on autoradiographs) on the short-axis sections. All infarcts (4 mm in minimum diameter) in seven rats were detected by pinhole SPET. The SPET images in rats with or without myocardial infarction were consistent with the findings of ARG and NBT staining. There were significant correlations between pinhole SPET and ARG with respect to the infarct size (r=0.933,P 〈0.001;n=15) and the relative radiotracer distribution (r=0.931,P 〈0.001; n=68). This study therefore confirmed the accuracy of myocardial pinhole SPET imaging in rats with myocardial infarction. This method may partially substitute for ARG and prove useful for assessing new myocardial imaging agents in vivo in small laboratory animals.
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  • 164
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    Cell & tissue research 286 (1996), S. 249-255 
    ISSN: 1432-0878
    Keywords: Key words: GDNF ; NT-4/5 ; Tachykinin ; Dopamine ; Amphetamine ; PPT-A ; Survival ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Glial-cell-line-derived neurotrophic factor (GDNF) is a novel trophic factor with potent trophic effects on several neuron populations in the central and peripheral nervous system. In the present study, we have investigated and compared the potential of dopamine and metamphetamine with that of the two striatal neurotrophic factors, viz., GDNF and neurotrophin-(NT)-4/5, to regulate substance P and its preprotachykinin-A mRNA in organotypic striatal slices from postnatal (day 10) rats. Incubation for 2 weeks with 10 ng/ml GDNF significantly increased substance-P-like immunoreactivity determined by radioimmunoassay. Similarly, the corresponding preprotachykinin-A mRNA increased after 1 and 2 weeks of incubation, as analyzed by in situ hybridization. NT-4/5 exhibited similar effects.The dopamine-releasing agent metamphetamine stimulated substance-P-containing neurons in 1-week-old striatal slices, whereas dopamine stimulated substance-P-like immunoreactivity in 1- and 2-week old striatal cultures. The effects of dopamine and GDNF were not additive. We conclude that substance-P-containing medium-sized spiny neurons in the striatum are under both dopaminergic and growth factor control by GDNF and NT-4/5, which are both synthesized in the striatum. This adds a previously unknown role to those that have been established for GDNF in the nigrostriatal system.
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  • 165
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    Medical molecular morphology 29 (1996), S. 28-36 
    ISSN: 1860-1499
    Keywords: Swimming test ; Skeletal muscle ; Rat ; Temperature ; Light and electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Structural changes in rat skeletal muscle induced by swimming to exhaustion were investigated by light and electron microscopy. Male Wistar rats were divided into four groups: a 28°C swimming groups, a 42°C swimming group, and non-swimming control groups at each of these temperatures. The experimental animals were tested in water for 32 min. Immediately after the swimming test, under pentobarbital intravenous anesthesia, the extensor digitorum longus muscle (EDL) and the soleus muscle (SOL) of each animal were removed from the right hindleg. Light microscopy revealed structural changes such as atrophy and focal necrosis in both muscles in animals swimming at 28 and 42°C. In some animals swimming at 42°C, an inflammatory reaction was noted around severely necrotic lesions in the EDL. A few structural changes indicative of mild atrophy were observed in the control animals. Electron microscopy revealed swelling of the sarcoplasm, swelling of the mitochondria, and disorganization or disappearance of myofilaments in various degrees in the atrophic and focal necrotic muscles of the animals swimming at 28 and 42°C. The degree of these structural changes in skeletal muscle fibers was more conspicuous in the animals swimming at 42°C than at 28°C, and more marked in the EDL than in the SOL.
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  • 166
    ISSN: 1439-6327
    Keywords: Short-term dietary change ; Glycogen Triacylglycerol ; Lipolysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of short-term diet change from high fat (F) to high carbohydrate (C) (or vice versa) on the storage and utilization of glycogen and triacylglycerol (TG) in muscle and liver were studied in untrained rats. Rats were fed on an F or C diet for 28 days. For an additional 3 days, half of the rats in both F and C groups were fed the same diets as before (F-F and C-C) and the other half of the rats were switched to the counterpart diets (F-C and C-F). On the final day of the experiment, half of the rats in each diet group were exercised by swimming for 1.5 h and the other half were rested. Short-term diet change from F to C diets increased, but the change from C to F diets decreased, glycogen stores of soleus and plantaris muscles and liver, resulting in no difference in glycogen stores between F-C and C-C, and between F-F and C-F. The dietary change also had an affect on TG stores of red gastrocnemius muscle and liver - however, muscle TG stores were still higher in F-C than in C-C and C-F, and there were no differences in liver TG stores between F-C and C-F. Exercise decreased muscle glycogen contents markedly in F-C and C-C, whereas, it decreased muscle TG concentrations in F-F and C-F. Liver glycogen depletion was lower in F-C than in other groups. Lipolytic activities of epididymal adipose tissue at rest and postexercise were no differences between F-F and F-C, and were higher in F-C than in C-C and C-F. β-adrenergic receptor binding was determined with [125I] iodocyanopindolol, and maximal numbers of β-adrenergic receptor of plasma membrane from perirenal adipose tissue were approximately 170%–200% higher in F-C than in other groups at rest and postexercise. These results suggested that short-term C diet fed rats adapted to F diet enhanced not only glycogen stores of muscle and liver but also did not decrease lipolytic activity of adipose tissue with increased β-adrenergic receptor density, resulting in the preservation of energy reserves (glycogen and TG) of muscle at rest, and liver glycogen sparing during exercise.
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  • 167
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    European journal of applied physiology 72 (1996), S. 496-501 
    ISSN: 1439-6327
    Keywords: Hyperthyroidism ; Glycogen ; Skeletal muscles ; Exercise ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the present study was to examine the rate of glycogen mobilization during exercise and the rate of the postexercise glycogen replenishment in different muscle types [white (WG), and red (RG) gastrocnemius, soleus (S) and diaphragm (D)] in rats treated with triiodothyronine (T3, group T). Rats of the control group (C) were treated with saline. The animals were made to run on a treadmill set at 0° gradient and at a speed of 1200 m·h−1. The time taken to reach exhaustion in group C was 188 (SD 23) min, whereas in group T, it was only 63 (SD 12) min. The content of glycogen in all muscles of the rats from group T at rest and during exercise was significantly lower than in group C at each corresponding time. At exhaustion, the glycogen content was in WG(C) 34.79 (SD 4.65), (T) 20.10 (SD 4.10); in RG(C) 22.82 (SD 4.66), (T) 16.50 (SD 2.00); in S(C) 14.85 (SD 2.48), (T) 11.90 (SD 2.93); in D(C) 18.18 (SD 3.49), (T) 7.54 (SD 3.36) (μmol of glucosyl units·g−1). The amount of glycogen mobilized during exhausting exercise in RG, S and D was similar in both groups whereas in WG it was much higher in rats of group T than in group C. The concentration of glycogen returned to pre-exercise values in each muscle 3 h after exercise. The net amount of glycogen resynthetized during 3 h of recovery depended on the muscle type. It was in WG(C) 3.30, (T) 18.03; in RG(C) 21.34, (T) 25.88, in S(C) 34.00, (T) 17.68, and in D(C) 17.25, (T) 12.22 μmol of glucosyl units·g−1 (each number represents the difference between the means). It concluded that treatment with T3 markedly affects this exercise-induced metabolism of glycogen in each muscle type. From our study it is suggested that low muscle glycogen content may contribute to a reduction in exercise performance in hyperthyroidism.
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  • 168
    ISSN: 1432-0878
    Keywords: Key words: Mineralization ; Matrix vesicles ; Dentine ; Ultrastructure ; Element analysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The purpose of this study was to elucidate the mineralization process of mantle dentine by ultrastructural and element-analytical investigation of matrix vesicles and successive stages. Upper second molars of albino rats were cryofixed and embedded in resin after freeze drying. Semithin dry sections were prepared for analyzing the calcium and phosphorus concentrations in the mineralized matrix vesicles or noduli, larger mineralized islands, and the mantle dentine. For ultrastructural studies, it was necessary to reduce section contact with hydrous fluids to a minimum in order to avoid preparation artifacts. The first mineral deposits were recognized as dot-like formations both in the interior of matrix vesicles and in association with the inner vesicle membrane. This indicated the existence of mineral nucleating sites located both at the inner membrane and at calcium-phosphate-binding macromolecules in the interior of the matrix vesicles. A significantly higher mineral content was found in mineralized matrix vesicles than in the mineralized extravesicular regions of the mineralized islands, suggesting the existence of a rapidly and densely mineralizing matrix in the matrix vesicles. A significant increase in mineral content per volume proceeding from the mineralized islands to mantle dentine suggested a further increase in the density of mineral.
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  • 169
    ISSN: 1433-2981
    Keywords: Rat ; Blood-brain barrier ; Development ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A mouse monoclonal antibody which specifically reacts with putative blood-brain barrier (BBB) competent endothelial cells of rat cerebral capillaries was used to identify barrier competent cells in the central nervous system (CNS). The development of the cerebral capillaries and the BBB was examined and quantified, from day 6 to day 40 postpartum, using immunocytochemical and unbiased stereological techniques. There was a progressive increase in capillary formation postnatally, with collateral branching observed with progressive age. BBB development was confined to individual endothelial cells located at the periphery of the cortex until day 10 postpartum. Antibody binding progressively increased postnatally, contributing 30% of the total capillary surface area by day 20. There was a rapid elevation of reactivity from day 20 to day 40, with a mean of 83% by day 40. The BBB constitutes minimal amounts of brain vascular capillaries before day 10 of life in the rat. There is a slower increase in BBB than in total capillaries between days 10 and 20. There is a reversal of this trend between days 20 and 40.
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  • 170
    ISSN: 1433-2981
    Keywords: Clinical chemistry ; Haematology ; Rat ; Sampling technique(s)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Blood samples from male and female rats were collected from four different sampling sites by the same technicians and analysed by the same procedures. The sampling sites were the abdominal aorta, orbital venous plexus, dorsal anastomotic orbital vein and sublingual vein. Values obtained in blood samples collected from peripheral sites were compared to those from the abdominal aorta, a sampling site which is normally unaffected by the sampling technique. There were significant differences in haematological parameters, particularly in leucocyte counts which were higher in samples collected from the peripheral sites than in those withdrawn from the central one. No significant changes were observed in coagulation parameters. A significant increase in clinical chemistry parameters related to soft tissue damage, namely creatinine kinase, lactate dehydrogenase, hydroxybutyrate dehydrogenase and aspartate aminotransferase, was seen in samples collected from both orbital sites. From this study it can be concluded that haematological and biochemical values obtained from rats in toxicological studies using different sampling sites are reliable both in males and females, provided that they are compared to values obtained from the same site in untreated controls. Sampling from the orbital plexus proved to be the least invasive method.
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  • 171
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    New York, NY : Wiley-Blackwell
    International Journal of Quantum Chemistry 57 (1996), S. 63-71 
    ISSN: 0020-7608
    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A new version of solutions in the form of an exponentially weighted power series is constructed for the two-dimensional circularly symmetric quartic oscillators, which reflects successfully the desired properties of the exact wave function. The regular series part is shown to be the solution of a transformed equation. The transformed equation is applicable to the one-dimensional problem as well. Moreover, the exact closed-form eigenfunctions of the harmonic oscillator can be reproduced as a special case of the present wave function. © 1996 John Wiley & Sons, Inc.
    Additional Material: 5 Tab.
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  • 172
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    International Journal of Quantum Chemistry 57 (1996), S. 139-139 
    ISSN: 0020-7608
    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 173
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    International Journal of Quantum Chemistry 57 (1996), S. 391-399 
    ISSN: 0020-7608
    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The wave function of a system may be expanded in terms of eigenfunctions of the N -1 electron Hamiltonian times one-particle functions known as generalized overlap amplitudes (GOAS). The one-electron operator whose eigenfunctions are the GOAS is presented, without using an energy-dependent term as in the one-particle Green function or propagator approach. It is shown that this operator and the extended Koopmans' theorem (EKT) one-electron operator are of similar form, but perform complementary roles. The GOA operator begins with one-electron densities and total energies of N -1 electron states to generate the two-matrix and total energy of an N-electron state. The EKT operator begins with the two-matrix of an N-electron state to generate one-electron densities and ionization potentials (or approximations thereto) for N -1 electron states. However, whereas the EKT orbitals must be linearly independent, no such restriction applies to the GOAS. © 1996 John Wiley & Sons, Inc.
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  • 174
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    International Journal of Quantum Chemistry 57 (1996), S. 959-970 
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    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Interactions of DNA bases frequently involve the DNA base amino groups. In contrast to the empirical force fields, the ab initio calculations predict nonplanar DNA base amino groups. The same conclusion also follows from the density functional theory (DFT) calculations. Both local and nonlocal density approximations were used. Optimized geometries of two other molecules with nonplanar amino groups (aniline, formamidine) are presented for comparison. The influence of nonplanar DNA base amino groups on the conformational variability of DNA is discussed. © 1996 John Wiley & Sons, Inc.
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  • 175
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    International Journal of Quantum Chemistry 57 (1996), S. 943-948 
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    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The conformational behavior and the stability of thiazolium and thiamin diphosphate (ThDP) adducts formed by the C2 addition of the substrates pyruvate and glyoxylate to the corresponding thiamin systems are investigated within the force-field version PIMM90 as well as the semiempirical AM1 and PM3 methods. Moreover, the reaction coordinate of the decarboxylation process of the adducts with respect to the C2α(SINGLEBOND)COO- bond are calculated by PM3 and AM1. The calculations on the key intermediates of the Breslow mechanism are performed in order to study the steric aspects of both substrate adducts that show a different pathway in the catalytic cycle. The alternative structural findings for the decarboxylation products are compared with first 6-31C* studies on the corresponding thiazolium model systems. Especially, the PM3 calculations show that the elimination of CO2 is favored if the arrangement of the carboxylate group is nearly perpendicular to the plane of the thiazolium ring. These results support the least-motion maximum-overlap mechanism in the enzymatic decarboxylation reaction, proposed by Kluger. The most stable conformers of the ThDP adducts and its decarboxylation products are characterized by V-like structures and the formation of a significant intramolecular hydrogen bonding under participation of the 4′-aminopyrimidine ring. © 1996 John Wiley & Sons, Inc.
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  • 176
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    International Journal of Quantum Chemistry 57 (1996), S. 971-974 
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    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Ab initio calculations were performed on the tautomers and conformers of N-hydroxyurea using a 6-31G** basis set. The minimum-energy structures have been found and the importance of the intramolecular hydrogen bond as the stabilizing factor was pointed out. © 1996 John Wiley & Sons, Inc.
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  • 177
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    International Journal of Quantum Chemistry 57 (1996) 
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    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
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  • 178
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    International Journal of Quantum Chemistry 57 (1996), S. 985-1018 
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    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 179
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    International Journal of Quantum Chemistry 57 (1996), S. 975-983 
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    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Many biological processes are characterized by an essentially quantum dynamical event, such as electron or proton transfer, in a complex classical environment. To treat such processes properly by computer simulation, allowing nonadiabatic transitions involving excited states, we recently developed a density matrix evolution (DME) method [H. J. C. Berendsen and J. Mavri, J. Phys. Chem, 97, 13464 (1993)] which simulates the dynamics of quantum systems embedded in a classical environment. The formalism of the method is presented and an overview of the applications ranging from collisions of a quantum harmonic oscillator with noble gas atoms to proton tunneling in a double-well hydrogen bond is given. The methodology for treatment of proton-transfer processes with inclusion of excited states is presented. Future application of the method on biologically interesting processes, such as proton transfer in enzymatic reactions, is discussed. © 1996 John Wiley & Sons, Inc.
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  • 180
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    International Journal of Quantum Chemistry 57 (1996), S. 1019-1031 
    ISSN: 0020-7608
    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: For theoretical reasons, and on account of the development of a new interpolation technique, it is useful and important to examine the asymptotic behavior of the solution to the one-dimensional Hubbard model. In this article, it is shown how perturbative expansions for the energy can be developed in the asymptotic region of the relevant coupling for all the relevant excited states of cyclic polyene rings. © 1996 John Wiley & Sons, Inc.
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  • 181
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    International Journal of Quantum Chemistry 57 (1996), S. 1049-1055 
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    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The simple BSSE-free SCF method (CHA/F) introduced in the previous parts of this series is extended to the case of three subsystems, which may be either three weakly interacting molecules or a bimolecular system described by using bond functions. The CHA/F formalism is formulated in a more transparent manner, indicating also a straightforward way for generalization to the case of an arbitrary number of subsystems. The illustrative calculations show the viability of using the CHA/F scheme for three-component systems. © 1996 John Wiley & Sons, Inc.
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  • 182
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    International Journal of Quantum Chemistry 57 (1996), S. 1033-1048 
    ISSN: 0020-7608
    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: One is often led, in quantum mechanics, to a perturbative solution of an eigenvalue problem, which is defined by a given Hamiltonian. The perturbative series for the energy which results will be a function of a coupling constant which appears in the Hamiltonian. In this article, the perturbative series for the energy of a state of a cyclic polyene ring which are valid for the small and large coupling limit of the model are used to construct algebraic functions. These algebraic functions are defined in terms of polynomials which are given as a function of the energy variable and coupling parameter and can be solved to give the energy as a function of coupling. It is found that relatively small polynomials give very good agreement with the exact values and that the accuracy of the results increases rapidly as the degree of the polynomial increases. The final goal of this and subsequent articles is to study energy levels in PPP models of planar conjugated hydrocarbons. In this article, we test an interpolant technique on the case of the one-dimensional Hubbard model, where an exact solution can be obtained by solving a system of nonlinear equations. In the case of the Hubbard model, the correlation effects are overestimated. Therefore, if the technique works for the Hubbard model, it is reasonable to assume that the technique would work even better for the PPP model. © 1996 John Wiley & Sons, Inc.
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  • 183
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    International Journal of Quantum Chemistry 57 (1996), S. 1057-1066 
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    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The Ising, small-bipolaron (ISB) theory is a strong-coupling theory of cuprate superconductivity which is based on the negative-U, Hubbard Hamiltonian. Its ground state is composed of (small) bipolarons and (small-bipolaron) holes with a vibronically induced, bipolaron-hole exchange interaction, JBH, between them. The energy gap, Δ(0), is taken to be equal to the dissociation energy of a small bipolaron and which, since it is defined spectroscopically, is not an order parameter. The application of the Ising mean-field theory to the highly degenerate ground-state yields a second-order phase change with kTC/2 = JBH and a real order parameter, Ω(T), which is valid over the entire temperature range from zero to TC. Near TC, the Ising free-energy functional takes the same form as does the Landau. In the presence of an electromagnetic field, the Ising functional is a generalization of the Ginzburg-Landau functional which employs a complex order parameter and which is invariant under the electromagnetic gauge transformation. The breaking of the gauge invariance yields the London theory of superconductivity. © 1996 John Wiley & Sons, Inc.
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  • 184
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    International Journal of Quantum Chemistry 57 (1996), S. 1067-1076 
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    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The solvent shift of the π* ← n transition of acetone in water, acetonitrile, and tetrachloromethane was calculated in a combined quantum mechanical - classical mechanical approach, using both dielectric continuum and explicit, polarizable molecular solvent models. The explicit modeling of solvent polarizability allows for a separate analysis of electrostatic, induction, and dispersion contributions to the shifts. The calculations confirm the qualitative theories about the mechanisms behind the blue shift in polar solvents and the red shift in nonpolar solvents, the solvation of the ground state due to electrostatic interactions being preferential in the former, and favorable dispersion interaction with the excited state, in the latter case. Good quantitative agreement for the solvent shift between experiment (+1,700, +400, and -350 cm-1 in water, acetonitrile, and tetrachloromethane, respectively) and the explicit solvent model (+1,821, +922, and -381 cm-1) was reached through a modest Monte Carlo sampling of the solvent degrees of freedom. A consistent treatment of the solvent could only be realized in the molecular solvent model. The dielectric-only model needs reparameterization for each solvent. © 1996 John Wiley & Sons, Inc.
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  • 185
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    International Journal of Quantum Chemistry 57 (1996), S. 1097-1106 
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    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: In density functional theory (DFT), a many-electron problem for the electron density in atoms may be reduced, according to the Kohn-Sham scheme, to a one-electron problem. In the present work, a variational model is proposed which leads, within some assumptions, to the set of equations describing the change of the electron density ρ and energy ε during the ionization process. It is shown that the one-electron density contributions are not necessarily spherically symmetric, but assume the symmetry which depends upon the symmetry of the positive field. A few nonspherically symmetric potentials are studied in the present article. The nonlinear differential equation for density r is formulated and solved for Coulombic, Fues-Kratzer, and Hartmann potentials. The solutions and some particular examples are presented. © 1996 John Wiley & Sons, Inc.
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  • 186
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    International Journal of Quantum Chemistry 57 (1996), S. 1107-1114 
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    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The cycloaddition reaction of FCH(double bond)C(double bond)O and NH2CH(double bond)NH leading to 2-azetidinone was studied theoretically at the level of RHF/6-31G and RHF/6-31G*. Two possible mechanisms via a gauche or trans intermediate were compared. The obtained results show that the reaction proceeds in a gauche manner much easier than in a trans one. © 1996 John Wiley & Sons, Inc.
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  • 187
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    International Journal of Quantum Chemistry 57 (1996), S. 1077-1096 
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    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The role of the asymptotic behavior of approximating sequences of electron densities ρn(r) in the calculation of one-electron properties is studied. Rigorous mathematical results in the frame of Hilbert spaces are used to prove the following facts: (i) Both the L2 convergence of wave functions ψn and the E convergence of the corresponding energies En guarantee the correctness of the limiting procedure limn→x ∫Ω s((overline)x(/overline)|ψn|2 d(overline)x(/overline) = ∫Ω s((overline)x(/overline))|ψ|2 d(overline)x(/overline) for the most frequently used operators s(x), Ω being any bounded region of the n-particle configuration space R3N; and (ii) the uniform boundedness of the sequence {ρn} together with both the L2 and E convergencies is sufficient to guarantee the correctness of the limiting procedure limn→x ∫∞0 s(r)ρnr2dr = ∫x0 s(r)ρr2 dr for most one-electron operators s(r) including the power moment operators rk which, for large k, are representative of the class of operators not relatively form-bounded by the Hamiltonian. The mathematical concept of uniform boundedness is used to give a characterization of the capability of {ρn} to reproduce the asymptotic behavior of the true electron density ρ and it is shown by means of numerical examples how a sequence {ρn} that does not reproduce the correct asymptotic behavior is not uniformly bounded and can give divergent expectation values of one-electron operators s(r) not relatively form-bounded by the Hamiltonian. © 1996 John Wiley & Sons, Inc.
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    International Journal of Quantum Chemistry 57 (1996), S. 1115-1119 
    ISSN: 0020-7608
    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: We performed electronic ab initio calculations of ion clusters simulating a piece of ionic crystal. Our main interest here is to estimate the (direct) energy band gap from the cluster energy levels. The model consists of a central cation surrounded by four shells of ions, with additional point charges embedding the cluster. We present results for the series of alkali halides with rock-salt structure. © 1996 John Wiley & Sons, Inc.
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  • 190
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    International Journal of Quantum Chemistry 57 (1996), S. 1133-1133 
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    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 191
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    International Journal of Quantum Chemistry 57 (1996), S. 1131-1131 
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    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 192
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    International Journal of Quantum Chemistry 57 (1996), S. 1121-1129 
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    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: We report on an isolated cluster approach to determine local electronic structures of TiO2 surfaces before and after formation of intrinsic defects, i.e., oxygen vacancies, at different crystallographic sites. In particular, isolated oxygen vacancies at bridging sites, isolated oxygen vacancies at in-plane sites and aggregated oxygen vacancies at bridging sites have been treated which lead to changes in the coordination of the adjacent Ti atoms. We find that electronic band gap states are only formed in the presence of fourfold coordinated Ti surface atoms. © 1996 John Wiley & Sons, Inc.
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    International Journal of Quantum Chemistry 58 (1996), S. 3-10 
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    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The quantum dynamics of prototypical three-level metastable system under external perturbations, both time-independent and time-dependent, are studied numerically as well as analytically. The regular Rabi oscillations generated in the system under a monochromatic perturbation are shown to develop additional features when the system has a metastable state. The autocorrelation function of ψ(t) reveals nondecaying, almost quasiperiodic, behavior in such systems. The Rabi oscillations turn more complex when a bichromatic perturbation with two incommensurate frequencies is allowed to interact with the three-level system, irrespective of the presence or absence of a metastable state. A rapid decay in the autocorrelation function of the wavefunction [ψ(t)] is observed in such cases. © 1996 Wiley & Sons, Inc.
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  • 194
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    International Journal of Quantum Chemistry 58 (1996), S. 11-21 
    ISSN: 0020-7608
    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The present knowledge of the monotonicity properties of the spherically averaged electron density ρ(r) and its derivatives, which comes mostly from Roothan-Hartree-Fock calculations, is reviewed and extended to all Hartree-Fock ground-state atoms from hydrogen (Z = 1) to uranium (Z = 92). In looking for electron functions with universal (i.e., valid in the whole periodic table) monotonicity properties, it is found that there exist positive values of α so that the function go(r; α) = ρ(r)/rα is convex, and g1(r;α) = -ρ′(r)/rα is not only monotonically decreasing from the origin but also convex. This is, however, not the case for the function g2(r; α) = ρ′(r)/rα. Additionally, the conditions which specify values for β such that the function gn(r; β) = (-1) ′ρ(n)(r)/rβ is logarithmically convex are obtained and numerically calculated for n = 0,1 in all neutral atoms below uranium. The last property is used to obtain inequalities of general validity involving three radial expectation values which generalize all the similar ones known to date, as well as other relationships among these quantities and the values of the electron density and its derivatives at the nucleus. © 1996 John Wiley & Sons, Inc.
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    International Journal of Quantum Chemistry 58 (1996), S. 23-28 
    ISSN: 0020-7608
    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Pekeris' solution for vibrational-rotational levels of the Morse potential includes the unphysical domain - ∞ 〈 r 〈 0 of the internuclear separation, just like Morse's solution for vibrational levels. In this article, the method of confinement in a box is implemented to obtain the vibrational-rotational J = 1 levels of Morse potentials in the physical domain 0 〈 r 〈 ∞, as well as the corresponding Franck-Condon factors. Applications to Li2 and AIO are presented as illustrations. © 1996 John Wiley & Sons, Inc.
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    International Journal of Quantum Chemistry 58 (1996), S. 29-39 
    ISSN: 0020-7608
    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Potential energy curves are calculated for O2-, O2, and O2+ at the CCSD, QCISD, CCSD(T), and QCISD(T) levels of theory using aug-cc-pVDZ and aug-cc-pVTZ basis sets with electron correlation built onto inversion symmetry constrained and relaxed UHF wave functions. The spectroscopic constant re, we, we, xe, Dj, and αe, are determined from the potential curves using standard second-order perturbation theory expressions and are compared with experimental values to assess the relative accuracy of the theoretical approaches. Comparison of corresponding symmetry-constrained and symmetry-relaxed calculations indicates that the CCSD method is generally superior to CCSD(T), QCISD, and QCISD(T) in recovering from a symmetry-broken reference function. © 1996 John Wiley & Sons, Inc.
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    International Journal of Quantum Chemistry 58 (1996), S. 41-46 
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    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Ab initio and density functional theory (DFT) methods have been applied to generated geometries of chemical systems built only from nitrogen and oxygen. The results of hybrid, local, and nonlocal DFT methods were compared with ab initio HF and MP2 methods. The suitability of DFT methods for modeling nitrogen-oxygen chemical systems is discussed. © 1996 John Wiley & Sons, Inc.
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  • 198
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    International Journal of Quantum Chemistry 58 (1996), S. 47-55 
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    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The alternative decomposition reactions CH2(OH)2 → CH2O + H2O and CH2(OH)2 + H2O → CH2O + 2H2O are investigated using the semiempirical PM3 as well as the ab initio HF/3-21G, HF/6-31G, HF/6-31G**, and MP2/6-31G** calculations. Reactants, products, and appropriate transition states are located on corresponding potential energy surfaces and compared with those reported in earlier studies. © 1996 John Wiley & Sons, Inc.
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  • 199
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    International Journal of Quantum Chemistry 58 (1996), S. 57-65 
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    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The simplest prototypical hydrogen transfer reaction, i.e., Ḣ+ H2 → H2 + Ḣ, is studied by the quantum-mechanical ab initio methods. Results reveal that during this reaction free valence which almost equals the square of the spin density develops on the migrating hydrogen atom. Bond orders are calculated using Mayer's formalism. Both the variations of bond orders and bond lengths along the reaction path are examined. Our analysis reveals that the bond formation and bond cleavage processes in this reaction are not perfectly synchronous. The bond cleavage process is slightly more advanced on the reaction path. © 1996 John Wiley & Sons, Inc.
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    International Journal of Quantum Chemistry 58 (1996), S. 67-84 
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    Keywords: Computational Chemistry and Molecular Modeling ; Atomic, Molecular and Optical Physics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A general scheme for theoretical treatment of organometallic reactivity is proposed. It is based upon the notion that the reactivity of a molecule is strongly affected by its coordination to metal-containing fragments. Based upon this idea we describe the large-scale organometallic reactions as reactions of the ligands in the coordination spheres of transition metal complexes. We propose here a quantum mechanical framework for analysis of effects of coordination on the reactivity and give several examples of qualitative energy profiles for reactions in the ligand spheres of transition metal complexes. © 1996 John Wiley & Sons, Inc.
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