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  • 2010-2014
  • 1990-1994  (10,030)
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  • 101
    Electronic Resource
    Electronic Resource
    Effect of clozapine upon schedule-induced polydipsia (SIP) resembles neither the actions of dopamine D1 nor D2 blockade (1993)
    Springer
    Psychopharmacology 113 (1993), S. 250-256 
    Details
    ISSN: 1432-2072
    Keywords: Schedule-induced polydipsia ; SIP ; Clozapine ; Raclopride ; SCH 23390 ; Dopamine D1 antagonist ; Dopamine D2 antagonist ; Major tranquilizers ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of clozapine (CLOZ) upon acquired schedule-induced polydipsia in rats were compared to the effects of the dopamine (DA) D1 antagonist SCH 23390 (SCH) and the DA D2 antagonist raclopride (RAC). All three compounds suppressed water consumption, but only SCH and RAC decreased drinking efficiency. SCH was the only compound with an effect on panel pressing (PP), causing suppression even at a dose without effect upon water intake. SCH also affected the temporal pattern of licking (TPL) at all doses, while clozapine, 10 mg/kg, only affected the pattern acutely, and raclopride was without effect. In conclusion, PP and the TPL are more sensitive to D1 than D2 blockade. While PP and the TPL are more sensitive than water intake to D1 blockade, the opposite is true for D2 blockade. It is possible to differentiate between DA D1/D2 antagonists and CLOZ in this model, focusing upon reduction in water consumption, with and without reduction in drinking efficiency. Furthermore, it is possible to differentiate between D1 and D2 blockade by analyzing water consumption, PP and the TPL.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245706
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  • 102
    Electronic Resource
    Electronic Resource
    Interactions between chronic haloperidol treatment and cocaine in rats: an animal model of intermittent cocaine use in neuroleptic treated populations (1993)
    Springer
    Psychopharmacology 110 (1993), S. 427-436 
    Details
    ISSN: 1432-2072
    Keywords: Haloperidol ; Cocaine ; Apomorphine ; Stereotypy ; Locomotor activity ; Sensitization ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This experiment investigated the possibility that rats maintained on chronic haloperidol treatment would show increased behavioral responsiveness to cocaine, similar to that observed in human stimulant abusers who are chronically treated with neuroleptics. Thus, the effects on locomotion and stereotyped behavior of intermittent injections of cocaine were investigated in female rats receiving chronic haloperidol treatment. Daily injections of haloperidol (0.2 mg/kg, IP) or vehicle were administered for 6, 12 or 18 days prior to the start of testing with cocaine and were then continued throughout cocaine testing. All rats received four doses of cocaine (0.0, 3.0, 7.5, or 15.0 mg/kg, IP) in random order with an intervening vehicle day between successive drug days. The four dose sequence of cocaine was repeated a total of four times. Initial cocaine administration produced dose dependent increases in locomotion and stereotyped behavior. When the sequence of cocaine doses was repeated, differences among treatment groups emerged. Groups treated with haloperidol exhibited heightened locomotion in response to cocaine and with repeated injections, showed a higher rate of behavioral sensitization than control animals. These differences in the behavioral response to cocaine were maintained for at least 2 months following termination of daily haloperidol treatment. In order to examine the mechanisms underlying this heightened responsiveness to cocaine, apomorphine-induced locomotion (dose range, 0–250 µg/kg, SC) was determined. Regardless of dose, rats treated with haloperidol showed different temporal patterns of locomotion in response to apomorphine suggesting that the increased response to cocaine was related to changes in dopaminergic receptor sensitivity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244649
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  • 103
    Electronic Resource
    Electronic Resource
    22–28 Khz ultrasonic vocalizations associated with defensive reactions in male rats do not result from fear or aversion (1993)
    Springer
    Psychopharmacology 111 (1993), S. 190-194 
    Details
    ISSN: 1432-2072
    Keywords: Ultrasonic vocalizations ; Defense ; Pain ; Fear ; Aversion ; Social interactions ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study was carried out to determine whether 22–28 kHz vocalizations emitted during intermale interactions in adult rats were related with a state of fear, aversion or resulted from painful stimulation. Vocalizations in the 22–28 kHz range were measured in male rats during non-aggressive and aggressive social interactions; when given foot shock with a partner; during non-aggressive social interactions after an injection of (i) acetic acid (1%, IP); (ii) pentylenetetrazol (20–30 mg/kg, IP) and (iii) lithium chloride (63.8 mg/kg, IP). Ultrasonic vocalizations were consistantly detected in all rats while the animals displayed defensive or submissive postures when tested as intruders confronted with offensive residents or when administered foot shocks. Only occasional vocalizations were emitted, even in the presence of a partner, when the animals had received other painful or aversive treatments. These data support the hypothesis that 22–28 kHz vocalizations during intermale interactions are associated with defensive postures and are not the consequence of a state of fear or aversion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245522
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  • 104
    Electronic Resource
    Electronic Resource
    Striatal regulation of morphine-induced hyperphagia: an anatomical mapping study (1993)
    Springer
    Psychopharmacology 111 (1993), S. 207-214 
    Details
    ISSN: 1432-2072
    Keywords: Feeding ; Striatum ; Nucleus accumbens ; Morphine ; Opiates ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Both systemic and intracranial administration of morphine can result in spontaneous feeding in nondeprived rats. The present investigation was conducted to examine the involvement of the striatum in this phenomenon. Morphine sulfate (0, 0.5, 1.0, 5.0, 10.0, and 20.0 µg/0.5 µl) was microinjected into five discrete striatal subregions in non-deprived rats: the nucleus accumbens, the ventromedial striatum, the ventrolateral striatum, the anterior dorsal striatum, and the posterior dorsal striatum. Feeding, drinking, locomotion, rearing, and food intake were measured over 4 h after infusion. Results indicate that the striatum is a heterogeneous structure with regard to the regulation of opiate-induced feeding behavior and locomotor activity. Morphine infusion into anteroventromedial regions including the nucleus accumbens resulted in a marked hyperphagia that was generally delayed in onset; much smaller increases or no change in feeding occurred after administration into more dorsal, lateral and posterior areas. It is hypothesized that there may exist within the striatum an anatomical gradient that is most sensitive to opiate-induced feeding within the anteroventromedial sector. Since this area has extensive connections with other brain sites sensitive to opiate-induced feeding, it may be a critical part of an opiatergic feeding system within the brain. In addition, a possible role for the anteroventromedial striatum in compulsive feeding and bulimia is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245525
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  • 105
    Electronic Resource
    Electronic Resource
    Attenuation of scopolamine-induced spatial memory deficits in the rat by cholinomimetic and non-cholinomimetic drugs using a novel task in the 12-arm radial maze (1993)
    Springer
    Psychopharmacology 111 (1993), S. 435-441 
    Details
    ISSN: 1432-2072
    Keywords: Radial maze ; Spatial memory ; Scopolamine ; Cholinomimetics ; ACE inhibitors ; Angiotensin II antagonists ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of cholinomimetic and non-cholinomimetic agents on spatial memory using a novel task in the 12-arm radial maze were investigated. The task was designed to reduce the tendency to use non-spatial strategies. Animals were repeatedly trained to retrieve food rewards from three arms, until a criterion level of performance was reached. Scopolamine (0.03 and 0.1 mg/kg SC), but not N-methylscopolamine (0.1 mg/kg SC) disrupted performance of this task. Physostigmine (0.3 mg/kg SC) and pilocarpine (30 mg/kg SC) completely reversed the deficit of performance produced by scopolamine. Furthermore, the ACE inhibitor Hoe 288 (10 nmol ICV) and the angiotensin AT1 receptor antagonist losartan (10 mg/kg SC) also significantly attenuated the scopolamine-induced deficit. These results show that this novel task in the radial maze is sensitive to the disruptive effects of scopolamine and can identify cognitive enhancing effects of both cholinomimetic and non-cholinomimetic drugs. Thus, this maze task provides a useful model for the evaluation of novel cognitive enhancing agents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02253533
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  • 106
    Electronic Resource
    Electronic Resource
    Chronic treatments with cholinoceptor drugs influence spatial learning in rats (1993)
    Springer
    Psychopharmacology 111 (1993), S. 508-511 
    Details
    ISSN: 1432-2072
    Keywords: Spatial learning ; Rat ; Muscarinic ; Nicotinic ; Receptors ; Chronic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Nicotine, scopolamine, oxotremorine, diisopropyl-fluorophosphate (DFP) and tetrahydroaminoacridine (THA) were administered chronically to different groups of rats in doses reported to alter central muscarinic and/or nicotinic receptro numbers. Beginning 24 h after final drug injection, the groups were compared to a vehicle control group on acquisition of a hidden platform position in the Morris water maze over 20 trials with a 30-min inter-trial interval. Chronic treatment with either nicotine or scopolamine significantly improved the rate of learning, but oxotremorine and DFP retarded learning and THA had no effect on learning. The chronic drug effects on behaviour were consistent with known effects of the injected drugs on muscarinic and nicotinic binding in the forebrain and on the sensitivity of frontal cortex neurones to iontophoretically applied cholinoceptor agonists. However, alternative explanations for the observed changes cannot be ruled out, since the drugs used are known to have a wide range of effects on other neurotransmitters.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02253544
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  • 107
    Electronic Resource
    Electronic Resource
    Quantitative assessment of the microstructure of rat behavior: I.f(d), The extension of the scaling hypothesis (1993)
    Springer
    Psychopharmacology 113 (1993), S. 177-186 
    Details
    ISSN: 1432-2072
    Keywords: Rat ; Behavior ; Microstructure ; Scaling measures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies demonstrated that drug effects on the movement sequences of rats in unconditioned motor activity paradigms can be quantified by scaling measures that describe the average relationship between a variable of interest and an experimental parameter. However, rats engage in a wide variety of geometrically distinct movements that can be influenced differentially by drugs. In this investigation, the extended scaling approach is presented to capture quantitatively the relative contributions of geometrically distinct movement sequences to the overall path structure. The calculation of the spectrum of local spatial scaling exponents,f(d), is based on ensemble methods used in statistical physics. Results of thef(d) analysis confirm that the amount of motor activity is not correlated with the geometrical structure of movement sequences. Changes in the average spatial scaling exponent,d, correspond to shifting the entiref(d) function, and indicate overall changes in path structure. With the extended scaling approach, straight movement sequences are assessed independently from highly circumscribed movements. Thus, thef(d) function identifies drug effects on particular ranges of movement sequences as defined by the geometrical structure of movements. More generally, thef(d) function quantifies the relationship between microscopically recorded variables, in this paradigm consecutive (x, y) locations, and the macroscopic behavioral patterns that constitute the animal's response topography.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245695
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  • 108
    Electronic Resource
    Electronic Resource
    Effect of acute and chronic diisopropylfluorophosphate and atropine administration on somatostatin binding in the rat frontoparietal cortex and hippocampus (1993)
    Springer
    Psychopharmacology 110 (1993), S. 103-109 
    Details
    ISSN: 1432-2072
    Keywords: Diisopropylfluorophosphate ; Atropine ; Somatostatin receptors ; Brain ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The acute and chronic administration of diisopropylfluorophosphate (DFP), an inhibitor of acetylcholinesterase (AChE), and of atropine, a blocker of muscarinic cholinergic receptors, did not affect somatostatin-like immunoreactivity (SLI) content in the frontoparietal cortex and hippocampus of rats. Acute and chronic DFP administration increased the number of specific125I-Tyr11-somatostatin (125I-Tyr11-SS) receptors in synaptosomes from the frontoparietal cortex but not in those from the hippocampus and did not change the affinity constant. This increase in125I-Tyr11-SS binding was not due to a direct effect of DFP on somatostatin (SS) receptors since no rise of binding was produced by high concentrations of DFP (10−5 M) when added in vitro. The increase could be blocked by pretreatment with atropine. The acute administration of atropine alone had no observable effect on the number of SS receptors. However, repeated atropine administration produced a significant decrease in the125I-Tyr11-SS binding in synaptosomes from the frontoparietal cortex but not in those from the hippocampus although the affinity constant was unchanged. The results suggest that interactions between somatostatinergic and cholinergic receptors may be important in the rat frontoparietal cortex.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246957
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  • 109
    Electronic Resource
    Electronic Resource
    In a drug discrimination procedure isolation-reared rats generalize to lower doses of cocaine and amphetamine than rats reared in an enriched environment (1993)
    Springer
    Psychopharmacology 110 (1993), S. 115-118 
    Details
    ISSN: 1432-2072
    Keywords: Cocaine ; Amphetamine ; Drug discrimination ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats with different behavioral histories, defined by rearing and housing in either an enriched condition (EC) or an isolation condition (IC), were trained in a two-lever operant procedure to discriminate 5.0 mg/kg cocaine from saline. In cocaine dose-generalization tests, the IC rats exhibited an ED50 (1.01 mg/kg) significantly lower than the EC rats (ED50:1.55 mg/kg). The cocaine-appropriate responding was emitted when the rats were treated withd-amphetamine, and for thed-amphetamine test doses the ED50 (0.19 mg/kg) was again significantly lower for the IC rats compared to the ECs (ED50:0.33 mg/kg). These data suggest that IC rats are more sensitive to the stimulus properties of indirect dopaminergic agonists than EC rats and highlight the importance of environmental variables in governing an organism's response to the stimulus properties of abused drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246959
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  • 110
    Electronic Resource
    Electronic Resource
    Intracellular pH in renal tubules in situ: single-cell measurements by confocal laserscan microscopy (1993)
    Springer
    Pflügers Archiv 422 (1993), S. 523-529 
    Details
    ISSN: 1432-2013
    Keywords: Confocal microscopy ; Fluorescence microscopy ; Proximal tubule ; 2′,7′-Bis(carboxyethyl)-5(6)-carboxyfluorescein ; Intracellular pH ; Viability ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Confocal laserscan microscopy with a dual-excitation device was used to record intracellular pH (pHi) regulation in rat proximal convoluted tubules microperfused in vivo. Cells were loaded with the pH-sensitive, fluorescent dye 2′,7′-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF). Single cells could be distinguished within the tubules and separate measurements were possible. Application of an NH4Cl pulse by peritubular perfusion caused an immediate increase in intracellular pH. Intraluminal injection of NH4Cl led to a slower increase in intracellular pH. In both cases, cessation of perfusion led to an immediate acidification. Peritubular perfusion with 300 μM 4,4′-diisothiocanatodihydrostilbene-2, 2′-disulphonic acid (H2DIDS) caused an intracellular alkalinisation. Microperfusion, pH-sensitive dyes and confocal laserscan microscopy provide a new non-invasive method to measure intracellular pH effectively in individual cells of near-surface structures of the intact kidney.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00375081
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  • 111
    Electronic Resource
    Electronic Resource
    Acute toxicity of two pyrethroids, permethrin, and cypermethrin in neonatal and adult rats (1993)
    Springer
    Archives of toxicology 67 (1993), S. 510-513 
    Details
    ISSN: 1432-0738
    Keywords: Pyrethroids ; Acute toxicity ; Drug metabolism inhibitors ; Neonatal ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study aims specifically at obtaining a comparison of the acute toxicity of cypermethrin (CY), a type I pyrethroid, and permethrin (PERM), a type II pyrethroid, administered orally as a single dose to neonatal and adult rats, and at assessing the importance of pyrethroid biotransformation in CY and PERM toxicity through use of drug metabolism inhibitors. Our experiments show that CY is more toxic than PERM to adult and neonatal rats. The sensitivity of neonatal rats both to CY and to PERM toxicity is higher, the younger the animals. CY is much more toxic than PERM in the neonatal rat, compared with the adult. In rats aged 8, 16, and 21 days, pretreatment with piperonil butoxide (PB), a monooxygenase inhibitor, or with tri-o-tolyl phosphate (TOTP), an esterase inhibitor, does not produce significant variations in the lethal effects of CY and PERM. Instead, in the adult rats, a significant increase in CY (X2=5.97;p〈0.05) and PERM (X2=4.37;p〈0.05) mortality occurred in rats pretreated with esterase inhibitors, whereas no increase in CY and PERM toxicity was found in adult animals pretreated with monooxygenase inhibitor. It was concluded that the higher level of sensitivity of the neonate rat to pyrethroid toxicity is probably due to incomplete development of the enzymes which catalyze the metabolism of pyrethroids in the liver of young animals. It is suggested that ester hydrolysis is an important pyrethroids detoxification reaction in the adult rat.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01969923
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  • 112
    Electronic Resource
    Electronic Resource
    Differences in the effects of model inducers of cytochrome P450 on the biotransformation of scoparone in rat and hamster liver (1993)
    Springer
    Archives of toxicology 67 (1993), S. 92-97 
    Details
    ISSN: 1432-0738
    Keywords: Rat ; Hamster ; Microsomes ; Scoparone ; Cytochrome P450 ; Species differences ; Induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The hamster is known to display very high rates of monooxygenase-mediated biotransformation. In comparison with other species little knowledge has been gathered with respect to the nature of its cytochrome P450 enzymes and their respective inducibility. We studied the consequences of induction of P450 enzymes in rats and Syrian golden hamsters using the regioselective oxidative O-demethylation of the coumarin derivative scoparone. This metabolic conversion indicates differential effects of P450 inducers in the rat, in which various types of inducers cause different shifts in the isoscopoletin/scopoletin metabolite ratio (I/S-ratio). Liver microsomes from hamster not treated with P450 inducers oxidized scoparone much more efficiently than liver microsomes of untreated rats. In rat liver microsomes total demethylation rates of scoparone increased upon in vivo treatment with phenobarbital or ß-naphthoflavone. Phenobarbital reduced the I/S-ratio whereas ß-naphthoflavone caused an increase in this ratio. In hamster liver microsomes both phenobarbital and β-naphthoflavone treatments resulted in a decrease in the I/S ratio. In this species the total scoparone demethylation rate was not much affected by phenobarbital, but β-naphthoflavone caused a huge increase in over-all scoparone biotransformation. In both species, dexamethasone, isoniazid and clofibrate were much less effective. In contrast to the rat, in the hamster the scoparone biotransformation profile cannot be used to differentiate between phenobarbital- or β-naphthoflavone-treated animals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01973677
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  • 113
    Electronic Resource
    Electronic Resource
    Electroretinographic assessment of early retinopathy in rats (1993)
    Springer
    Archives of toxicology 67 (1993), S. 120-125 
    Details
    ISSN: 1432-0738
    Keywords: Amoscanate ; Retinal degeneration ; Rat ; Electroretinography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Amoscanate, a substance which damages photoreceptors, was administered orally to Wistar rats in doses of 10, 40, and 125 mg/kg body weight once daily for 3 or 10 days. At both times electroretinographic, ophthalmological, and histopathological examinations of the retina were carried out to compare the sensitivity of conventional methods and to test electroretinography (ERG) for suitability for use in toxicity studies. Time-dependent and dose-dependent effects were found by electroretinography and light microscopy. However, signs of retinal changes appeared earlier and more distinctly in the electroretinogram. Ophthalmological fundus examination in albino rats yielded no characteristic correlate. In conclusion, electroretinography constitutes a valuable supplement to histopathology and is suitable for use in toxicity studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01973682
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  • 114
    Electronic Resource
    Electronic Resource
    Evaluation of DNA damage by alkaline elution technique after inhalation exposure of rats and mice to 1,3-butadiene (1993)
    Springer
    Archives of toxicology 67 (1993), S. 34-38 
    Details
    ISSN: 1432-0738
    Keywords: Alkaline elution ; 1,3-Butadiene ; Lung ; Liver ; Mouse ; Rat ; Single-strand breaks ; DNA-DNA cross-links ; DNA-protein cross-links
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The alkaline filter elution technique was used to evaluate single strand breaks (SSB), DNA-DNA (DDCL) and DNA-protein cross-links (DPCL) in liver and lung of male rats (Sprague-Dawley) and male mice (B6C3F1) after exposure to 2000 ppm 1,3-butadiene (BD) for 7 days (7 h/day and/or to 100, 250, 500, 1000) 2000 ppm BD for 7 h. SSB were detected in liver DNA of both species at 2000 ppm. Cross-links are more pronounced in mouse lung than in mouse liver. Elution rates of lung DNA from mice exposed for 7 h to different concentrations of BD revealed an increase in cross-links between 250 and 500 ppm, and a further increase in cross-links up to 2000 ppm. No such signs of genotoxicity could be observed for the lung of rats. Our data support the involvement of reactive metabolites (epoxybutene and especially diepoxybutane) in butadieneinduced carcinogenesis in the mouse but not to that extent in the rat.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02072032
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  • 115
    Electronic Resource
    Electronic Resource
    Effect of pretreatment with CBDP on the toxicokinetics of soman stereoisomers in rats and guinea pigs (1993)
    Springer
    Archives of toxicology 67 (1993), S. 706-711 
    Details
    ISSN: 1432-0738
    Keywords: C(±)P(±)-Soman ; Toxicokinetics ; 2-(o-cresyl)-4H-1∶3∶2-benzodioxaphosphorin-2-oxide ; CBDP ; Carboxylesterase ; Rat ; Guinea pig ; Marmoset
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pretreatment of rats and guinea pigs with the specific carboxylesterase inhibitor 2-(o-cresyl)-4H-1 ∶ 3 ∶ 2-benzodioxaphosphorin-2-oxide (CBDP) reduces the LD50 of the nerve agent C(±)P(±)-soman in these species to the same range as in primates. This suggests that such CBDP-pretreated animals can be used in investigations that are relevant for prophylaxis and therapy of intoxication with C(±)P(±)-soman in primates including humans. In order to test this hypothesis we have studied the toxicokinetics of the toxic C(±)P(−)-isomers of soman in artificially respirated and CBDP-pretreated rats and guinea pigs at intravenous doses corresponding to 6 × LD50. A comparison of the areas under the curve (AUCs) of the blood levels of C(±)P(−)-soman in pretreated and non-pretreated animals at the same absolute dose shows extreme nonlinearity with dose, indicating that CBDP occupies highly reactive binding sites which are no longer available for sequestration of the soman isomers. The AUCs of C(±)P(−)-soman at equitoxic doses of 6× LD50 are reduced by pretreatment with CBDP from 1683 to 464 ng.min.ml−1 in rats and from 978 to 176 ng.min.ml−1 in guinea pigs, which is in the range of the AUC in non-pretreated marmosets at an equitoxic dose (419 ng.min.ml−1). The blood levels of the C(±)P(−)-isomers in marmosets and CBDP rats are rather similar during the first 7 min, but persist in CBDP rats for 2 h longer at toxicologically relevant levels than in marmosets. The levels of C(±)P(−)-soman in CBDP-pretreated guinea pigs are substantially lower than in marmosets for an initial period of 80 min. Nevertheless, they drop below toxicologically relevant levels approximately 50 min later than in marmosets. Evidently, one should be cautious in considering CBDP, pretreated rats and guinea pigs as substitute primates.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01973695
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  • 116
    Electronic Resource
    Electronic Resource
    Toluene metabolism in isolated rat hepatocytes: effects of in vivo pretreatment with acetone and phenobarbital (1993)
    Springer
    Archives of toxicology 67 (1993), S. 107-112 
    Details
    ISSN: 1432-0738
    Keywords: Toluene ; Ethanol ; Metabolism ; Hepatocytes ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Hepatocytes isolated from control, acetone- and phenobarbital-pretreated rats were used to study the metabolic conversion of toluene to benzyl alcohol, benzaldehyde, benzoic acid and hippuric acid at low (〈100 μM) and high (100–500 μM) toluene concentrations. The baseline formation rates of toluene metabolites (benzyl alcohol, benzoic acid and hippuric acid) were 2.9±01.7 and 10.0±2.3 nmol/mg cell protein/60 min at low and high toluene concentrations, respectively. In vivo pretreatment of rats with acetone and phenobarbital increased the formation of metabolites: at low toluene concentrations 3- and 5-fold, respectively; at high toluene concentrations no significant increase (acetone) and 8-fold increase (phenobarbital). Apparent inhibition by ethanol, 7 and 60 mM, was most prominent at low toluene concentrations: 63% and 69%, respectively, in control cells; 84% and 91% in acetone-pretreated cells, and 32% (not significant) and 51% in phenobarbital-pretreated cells. Ethanol also caused accumulation of benzyl alcohol. The apparent inhibition by isoniazid was similar to that of ethanol at low toluene concentrations. Control and acetone-pretreated cells were apparently resistant towards metyrapone; the decrease was 49% and 64% in phenobarbital-pretreated cells at low and high toluene concentrations, respectively. In these cells, the decrease in presence of combined ethanol and metyrapone was 95% (low toluene concentrations). 4-Methylpyrazole decreased metabolite formation extensively in all groups. Benzaldehyde was only found in the presence of an aldehyde dehydrogenase inhibitor. Increased ratio benzoic/hippuric acid was observed at high toluene concentrations. These results demonstrate that toluene oxidation may be studied by product formation in isolated hepatocytes. However, the influence of various enzymes in the overall metabolism could not be ascertained due to lack of inhibitor specificity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01973680
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    A physiologically based pharmacokinetic model for butadiene and its metabolite butadiene monoxide in rat and mouse and its significance for risk extrapolation (1993)
    Springer
    Archives of toxicology 67 (1993), S. 151-163 
    Details
    ISSN: 1432-0738
    Keywords: 1,3-Butadiene ; Closed-chamber technique ; 1,2-Epoxybutene-3 ; Glutathione ; Glutathione turnover ; Inhalation ; Mouse ; Pharmacokinetics ; Physiological model ; Ping-pong mechanism ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The gas 1,3-butadiene (BU) is an important industrial chemical and an environmental air pollutant. BU has been shown to be a weak carcinogen in the rat but a potent carcinogen in the B6C3F1 mouse. This species difference makes risk extrapolation to humans difficult and the underlying mechanism should be clarified before meaningful risk extrapolation to humans can be made. One possible explanation for the species differences in cancer response is that there are quantitative species differences in the formation of genotoxic epoxides. To investigate this possibility a physiologically based pharmacokinetic (pbpk) model for BU together with its first reactive metabolite l,2-epoxybutene-3 (butadiene monoxide, BMO) was developed. Previously reported values on hepatic glutathione (GSH) turnover, depletion of hepatic GSH in rodents exposed to BU, and in vitro metabolic data of BU and BMO were included in the model, which incorporates intrahepatic first-pass hydrolysis of BMO and the ordered sequential, ping-pong mechanism to describe the enzyme kinetics of BMO-GSH conjugation. In vitro studies were carried out to obtain tissue: air partition coefficients of BU and BMO in rat tissue homogenates. The simulated pharmacokinetics of BU, BMO, and GSH agreed with previously published experimental observations in rat and mouse obtained in closed and open chamber experiments. According to the model, the internal dose of BMO (expressed either as the concentration in mixed venous blood or as the area under the concentration-time curve) is approximately 1.6 times higher in the mouse than in the rat for exposure to BU below 1000 ppm. At higher exposure levels, GSH depletion occurs in the mouse, but not in the rat, after about 6–9 h. This GSH depletion results in up to 2–3 times higher internal doses in the mouse than in the rat. The clear but relatively small species difference in body burdens of BMO indicated from our model can only partly explain the marked species difference in cancer response between mice and rats exposed to BU.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01973302
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    The cortical epithelium of the rat thymus after in vivo exposure to bis(tri-n-butyltin)oxide (TBTO) (1993)
    Springer
    Archives of toxicology 67 (1993), S. 186-192 
    Details
    ISSN: 1432-0738
    Keywords: Bis(tri-n-butyltin)oxide ; TBTO ; Thymus ; Epithelium ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Bis(tri-n-butyltin)oxide (TBTO) induces cortical atrophy in the rat thymus. We studied the potential involvement of the cortical epithelium in TBTO-induced thymotoxicity by (immuno) histology and electron microscopy. Juvenile male Wistar rats were orally intubated once with either 30 or 90 mg/kg TBTO and sacrificed 4 or 10 days later. A dose-dependent thymic atrophy occurred. Anti-keratin labelling showed epithelial cell aggregation in some animals at 10 days after exposure to 90 mg/kg TBTO, when recovery of the thymus was apparent. At the ultrastructural level, a relative shift was observed from “pale” to darker epithelial cell subtypes at the 30 mg/kg dose level, both at day 4 and day 10 after intubation. This phenomenon was not observed after exposure to 90 mg/kg TBTO. Both the altered keratin distribution and the increased electron density of the epithelium probably represent non-specific phenomena. The present morphological observations support the concept that TBTO affects the thymus via its action on lymphoid cells rather than on the epithelial compartment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01973306
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  • 119
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    Ultrastructure of the cortical epithelium of the rat thymus after in vivo exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (1993)
    Springer
    Archives of toxicology 67 (1993), S. 558-564 
    Details
    ISSN: 1432-0738
    Keywords: 2,3,7,8-Tetrachlorodibenzo-p-dioxin ; TCDD ; Thymus ; Epithelium ; Ultrastructure ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is known for inducing cortical atrophy in the rat thymus. The present study was conducted to provide ultrastructural evidence for the cortical epithelium to be a target for TCDD in vivo. Juvenile male Wistar rats were orally intubated once with either 50 or 150 μg/kg TCDD and killed 4 or 10 days thereafter. Major changes were found in the cortical thymic epithelium. First, a relative shift occurred from “pale” to darker cortical epithelial cell types, as judged by their nuclear and cytoplasmic electron density. This effect was most prominent at 10 days after exposure to 150 μg/kg TCDD. The increased electron density of the cortical epithelium indicates an altered state of cellular differentiation. Secondly, at the 150 μg/kg dose level focal epithelial cell aggregates were seen both at day 4 and day 10 after administration. This aggregation may either be compound induced or represent a secondary event to the collapse of the thymic stroma. Thirdly, increased vacuolation of cortical epithelial cells was apparent. This effect is interpreted as a consequence rather than a cause of thymocyte depletion from the cortex. This study indicates that TCDD exposure affects the cortical epithelium of the rat thymus at a high dose level. Electron microscopy reveals that the differentiation of epithelial cells is altered. In addition, epithelial cell aggregates are formed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01969269
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    Renal toxicity of aristolochic acid in rats as an example of nephrotoxicity testing in routine toxicology (1993)
    Springer
    Archives of toxicology 67 (1993), S. 307-311 
    Details
    ISSN: 1432-0738
    Keywords: Aristolochic acid ; Nephrotoxicity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The nephrotoxic action of aristolochic acid (AA) was investigated in female Wistar rats given single doses of 10, 50 or 100 mg/kg by gastric tube. Renal lesions developed within 3 days, the effect being dose-dependent. Histologically, there was evidence of necrosis of the epithelium of the renal tubules, and functionally, there were rises in plasma creatinine and urea together with increases in urinary glucose, protein, N-acetyl-β-glucosaminidase, gammaglutamyl transferase and malate dehydrogenase. Taking AA as an example, the aim of the present study was to consider the suitability of this model, based on a combination of histology and laboratory investigations, as a short-term test for the detection of nephrotoxic agents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01973700
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  • 121
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    Species-specific pharmacokinetics of styrene in rat and mouse (1993)
    Springer
    Archives of toxicology 67 (1993), S. 517-530 
    Details
    ISSN: 1432-0738
    Keywords: Pharmacokinetics ; Styrene ; Diethyl dithiocarbamate ; Species scaling ; Allometric extrapolation ; Mouse ; Rat ; Man ; Closed chamber technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pharmacokinetics of styrene were investigated in male Sprague-Dawley rats and male B6C3F1 mice using the closed chamber technique. Animals were exposed to styrene vapors of initial concentrations ranging from 550 to 5000 ppm, or received intraperitoneal (i.p.) doses of styrene from 20 to 340 mg/kg or oral (p.o.) doses of styrene in olive oil from 100 to 350 mg/kg. Concentration-time courses of styrene in the chamber atmosphere were monitored and analyzed by a pharmacokinetic two-compartment model. In both species, the rate of metabolism of inhaled styrene was concentration dependent. At steady state it increased linearly with exposure concentration up to about 300 ppm; more than 95% of inhaled styrene was metabolized and only small amounts were exhaled unchanged. At these low concentrations transport to the metabolizing enzymes and not their metabolic capacity was the rate limiting step for metabolism. Pharmacokinetic behaviour of styrene was strongly influenced by physiological parameters such as blood flow and especially the alveolar ventilation rate. At exposure concentrations of styrene above 300 ppm the rate of metabolism at steady state was progressively limited by biochemical parameters of the metabolizing enzymes. Saturation of metabolism (Vmax) was reached at atmospheric concentrations of about 700 ppm in rats and 800 ppm in mice, Vmax being 224 μmol/(h·kg) and 625 μmol/(h·kg), respectively. The atmospheric concentrations at Vmax/2 were 190 ppm in rats and 270 ppm in mice. Styrene accumulates preferentially in the fatty tissue as can be deduced from its partition coefficients in olive oil∶air and water∶air which have been determined in vitro at 37°C to be 5600 and 15. In rats and mice exposed to styrene vapors below 300 ppm, there was little accumulation since the uptake was rate limiting. The bioaccumulation factor body:air at steady state (K′st*) was rather low in comparison to the thermodynamic partition coefficient body:air (Keq) which was determined to be 420. K′st* increased from 2.7 at 10 ppm to 13 at 310 ppm in the rat and from 5.9 at 20 ppm to 13 at 310 ppm in the mouse. Above 300 ppm, K′st* increased considerably with increasing concentration since metabolism became saturated in both species. At levels above 2000 ppm K′st* reached its maximum of 420 being equivalent to Keq. Pretreatment with diethyldithiocarbamate, administered intraperitoneally (200 mg/kg in rats, 400 mg/kg in mice) 15 min prior to exposure of styrene vapours, resulted in effective inhibition of styrene metabolism, indicating that most of the styrene is metabolized by cytochrome P450-dependent monooxygenases. In order to simulate chronic exposure rats and mice were exposed to 150 and 500 ppm styrene on 5 consecutive days (6 h/day). On day 6, inhalation kinetics were studied. No change in the rate of styrene metabolism was detected compared to non-pretreated controls. Intraperitoneal administration of styrene to rats and mice led to concentration-time courses in the atmosphere of the closed chamber with agreed with those predicted by the applied pharmacokinetic model. After p.o. administration of styrene to rats and mice concentration time-courses showed considerable inter-animal variability. The pharmacokinetic model was extended by a first order absorption from the gastrointestinal tract with half-lives of 0.87 h (rat) and 0.41 h (mouse) to obtain reasonable fits through the measured data. The pharmacokinetic parameters of inhaled styrene were extrapolated allometrically from rat to mouse and from rat and mouse to man. A good agreement was obtained with experimentally determined values indicating similar pharmacokinetic behaviour of styrene in these species.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01969264
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    Thymocyte apoptosis as a mechanism for tributyltin-induced thymic atrophy in vivo (1993)
    Springer
    Archives of toxicology 67 (1993), S. 231-236 
    Details
    ISSN: 1432-0738
    Keywords: Tributyltin ; Thymic atrophy ; Immunotoxicity ; Apoptosis ; In vivo ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tributyltin (TBT) immunotoxicity in rodent species is primarily characterised by T-lymphocyte deficiency resulting from a depletion of cortical thymocytes. In this study, bis(tri-n-butyltin) oxide (TBTO) was administered to male rats as a single oral dose of 30 or 60 mg/kg, and assessments were made of thymic cytopathology and the integrity of cellular DNA. TBTO treatment did not cause severe toxicity or overt clinical signs; however, by 48 h post-dosing relative thymus weights at 30 and 60 mg/kg were reduced to 66 and 43%, respectively, of control values. Increased DNA fragmentation was evident in thymic cell isolates (principally thymocytes) obtained from treated animals during the period of thymic involution. When DNA purified from these cells was visualised by agarose gel electrophoresis a multimeric internucleosomal fragmentation pattern, indicative of supra-physiological levels of apoptosis, was detected. Although unassociated apoptotic or necrotic thymocytes were essentially absent in cell preparations from TBTO-treated rats, significantly increased numbers of mononuclear phagocytic cells were observed. Many of these cells contained either apoptotic thymocytes, with nuclear morphologies exhibiting chromatin condensation, or cell remnants which were characterised as apoptotic bodies. Dibutyltin, which is a major metabolic dealkylation product of tributyltin, failed to significantly stimulate apoptosis when added to isolated thymocytes in vitro. Collectively, these findings suggest that activation of apoptosis contributes to TBT-induced thymocyte depletion in vivo, and indicate that it is unlikely that the metabolite dibutyltin is responsible for this effect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01974341
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    Experimental approaches towards testicular autotransplantation (1993)
    Springer
    European journal of pediatrics 152 (1993), S. S47 
    Details
    ISSN: 1432-1076
    Keywords: Rat ; Rabbit ; Contralateral damage ; Fertility ; Microvascular patency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An experimental approach was designed to analyse the outcome of testicular autotransplantation after microsurgery of arteries with 0.3–0.6 mm diameter in two different animal species. In particular, the patency of the anastomosis of the vessels, as well as testicular histology and fertility, was studied. In rats as well in rabbits, we could not observe contralateral damage after testicular autotransplantation. With the rabbit model, we can achieve a fertility rate of 37.5%; but only when we have a good patent anastomosis. Whereas, the rat model is good for surgical training of microvascular anastomosis; the quality of the microanastomosis shows no correlation to the testicular histology of the transplanted testis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02125439
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  • 124
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    Yeast single copy gene URP1 is a homolog of rat ribosomal protein gene L21 (1993)
    Springer
    Current genetics 23 (1993), S. 15-18 
    Details
    ISSN: 1432-0983
    Keywords: Yeast ; Rat ; Ribosomal protein ; 60S Ribosomal subunit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary This communication reports on a single-copy gene of Saccharomyces cerevisiae which is homologous to the rat ribosomal protein gene L21. The yeast and the rat genes show 59% identity in DNA sequences and in the predicted protein sequences. This yeast gene is, therefore, assumed to code for an as yet unassigned ribosomal protein (URP1). The URP1 open reading frame is 480 nucleotides long and can encode a protein of about Mr 18 200. Like most of the other known ribosomal protein genes, URP1 is interrupted by an intron in its 5′ terminal part and it is preceeded by upstream sequence elements which usually regulate transcription of these genes. Northern blot analysis reveals that the URP1 gene is actually expressed in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00336743
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    Differentiation of the rat myelomonocytic leukemia cell line c-WRT-7 by in vitro culture with the rat bone marrow preadipocyte cell line REC A16 (1993)
    Springer
    Journal of cancer research and clinical oncology 119 (1993), S. 335-341 
    Details
    ISSN: 1432-1335
    Keywords: Differentiation ; Leukemia cell ; Stromal cell ; Colony-stimulating factor ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Differentiation of the rat myelomonocytic leukemia cell line (c-WRT-7) was investigated, by co-culture with a rat embryonic bone marrow preadipose cell line (REC A16). Co-cultivation with REC A16, or with conditioned medium from REC A16 cultures (REC-CM), induced differentiation of c-WRT-7 cells to macrophages. A soluble factor(s) produced by REC A16 appeared to be responsible for the differentiation of c-WRT-7. Because REC-CM was associated with colony-stimulating activity on murine marrow progenitors, c-WRT-7 cells were cultured with various colony-stimulating factors (CSF) and it was found that macrophage CSF (M-CSF) significantly induced differentiation of c-WRT-7. We further demonstrated that both the colonystimulating and differentiation-inducing activities of REC-CM were significantly blocked by anti-M-CSF antiserum. These results suggest that the differentiation of c-WRT-7 is due to M-CSF produced by REC A16. Co-culture of these two cell lines should provide a useful model to study the mechanisms of interaction between leukemia cells and marrow stroma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01208841
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    Circadian rhythm of glucose utilization in the pineal body of rats of different ages (1993)
    Springer
    Child's nervous system 9 (1993), S. 25-27 
    Details
    ISSN: 1433-0350
    Keywords: Pineal gland ; Glucose metabolism ; Quantitative autoradiography ; Rat ; Development ; Aging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Employing quantitative autoradiography, pineal body glucose utilization (GU) was measured in daytime or at night in prepubertal (aged 1 month), adult (aged 3 months), and mature (over 12 months old) rats. In prepubertal and adult rats, in daytime, GU values within the pineal tissue were homogeneously distributed around 65 μmol glucose/100 g per min. In prepubertal animals no significant variations in GU were observed between daytime and nocturnal measurements. A circadian metabolic rhythmicity was evident in adult rats, with a GU peak measured at 2 a.m. In mature animals, GU also varied between day and night, with an increment in the relative difference between the two values. The present investigation is the first to demonstrate that circadian metabolic rhythmicity is absent before sexual maturation while it is enhanced in 12-month-old rats. These changes in pineal energy metabolism with advancing age are intriguing in view of the concept that the pineal gland may be involved in functional changes occurring during the process of aging.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00301931
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    Discriminative stimulus properties of a new anxiolytic, DN-2327, in rats (1993)
    Springer
    Psychopharmacology 110 (1993), S. 280-286 
    Details
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Generalization ; Antagonism ; DN ; 2327 ; Diazepam ; Buspirone ; Pentobarbital ; Pentylenetetrazol ; Benzodiazepine antagonist ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In an operant learning lever-pressing procedure on an FR10 schedule of milk reinforcement, male Wistar rats were trained to discriminate between saline and 3 mg/kg IP DN-2327, a new anxiolytic which acts on benzodiazepine receptors, 3 mg/kg IP diazepam or 15 mg/kg IP pentylenetetrazol (PTZ). More than 80% appropriate lever responding was established after 27, 38 and 44 daily training sessions with DN-2327, diazepam and PTZ, respectively, as the training drug. Although rats trained with DN-2327 dose-dependently generalized to various doses of DN-2327 and diazepam, the cue of DN-2327 was more potent than that of diazepam: ED50 values of DN-2327 and diazepam for stimulus generalization were 0.30 and 0.66 mg/kg, respectively. These animals partially generalized to pentobarbital (1–10 mg/kg) but did not generalize to buspirone (0.1–10 mg/kg). Rats trained with diazepam dose-dependently generalized to various doses of DN-2327, diazepam and pentobarbital with ED50 values of 0.51, 0.47 and 4.5 mg/kg, respectively, but did not generalize to buspirone. In rats trained with PTZ, DN-2327 and diazepam antagonized the discriminative stimulus produced by 15 mg/kg PTZ in a dose-dependent manner with ED50 values of 0.27 and 0.83 mg/kg, respectively, but buspirone neither antagonized nor was able to substitute for the PTZ-induced stimulus. The cue of DN-2327 was antagonized by flumazenil dose-dependently as was that of diazepam. Diazepam and pentobarbital reduced the total number of responses in all animals at 10 mg/kg, and buspirone did so at more than 3 mg/kg, while DN-2327 did not affect the total number of responses from 0.1 to 10 mg/kg. In conclusion, the cue of DN-2327 is similar to and more effective than that of diazepam; moreover, it is quite different from that of buspirone. In addition, the similarity of the interoceptive stimuli of DN-2327 and diazepam may suggest that they are not related to muscle relaxant and sedative properties, since the two drugs differ in this respect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02251282
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    Potentiation by low doses of selected neuroleptics of food-induced conditioned place preference in rats (1993)
    Springer
    Psychopharmacology 110 (1993), S. 460-466 
    Details
    ISSN: 1432-2072
    Keywords: Conditioned place preference ; Hedonia ; Food ; Dopamine ; Neuroleptics ; Autoreceptors ; Incentive learning ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Numerous data support the hypothesis that dopamine (DA) plays a crucial role in reward-related processes and in incentive learning in animals and man. The possibility that various neuroleptics exhibiting a high affinity for the dopaminergic D2 (and D3) receptors could reinforce DA transmission was studied using the conditioned place preference paradigm (CPP) in rats. This was done by examining the ability of these compounds to potentiate the reinforcing properties of food in hungry rats subjected to a version of the CPP paradigm which consisted of repeated pairings of food with a single environmental cue, the floor texture of an open field. During the test session when food was no longer available in the open field, the increase in the time spent by drug-free rats on the food-paired texture was assumed to indicate the perceived rewarding value of the food. This time was significantly lengthened when the specific D2 (D3)-receptor antagonists sulpiride (4 mg/kg), amisulpride (0.5, 1 mg/kg) or pimozide (0.03, 0.06 mg/kg) were administered before the food conditioning sessions. Larger doses of these compounds as well as haloperidol, metoclopramide and the non-specific D1-D2 antagonist, chlorpromazine, regardless of the doses tested, did not exhibit this effect, but rather reduced the food-induced CPP, an action usually associated with neuroleptics. The positive effects of amisulpride was reversed by a D1 receptor antagonist, SCH 23390 (0.01 mg/kg). These results suggest that, as with amphetamine (0.5 mg/kg), some D2-specific neuroleptics enhance the incentive value of food in a narrow range of low doses, an effect proposed to reflect a “prohedonic” property. The potentiation of the release of DA unconditionally evoked by food, through a selective blockade of the release-modulating D2-autoreceptors, could constitute the neurobiological substratum of this effect. A concomitant blockade of either D2 or D1 postsynaptic receptors, however, appeared to be sufficient to counteract such activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244653
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    Phencyclidine disrupts long- but not short-term memory within a spatial learning task (1993)
    Springer
    Psychopharmacology 111 (1993), S. 85-90 
    Details
    ISSN: 1432-2072
    Keywords: Phencyclidine ; Spatial learning test ; Memory disruption ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the first experiment rats with 1, 2, 3 or 4 mg/kg phencyclidine (PCP), or saline injections were tested for acquisition or retention of a cheese board spatial task (dry land version of a water maze). Results indicate that relative to controls or rats with injections of 1 and 2 mg/kg PCP, rats with 3 or 4 mg/kg PCP injections were impaired in acquisition and retention of the task as measured by increased distances traveled to find the correct food location. This impairment was primarily observed in between days but not within days performance. In the second experiment rats with 4 mg/kg PCP or saline injections were tested for memory performance of a delayed spatial matching-to-sample task. Results indicate that relative to controls rats with 4 mg/kg PCP injections were not impaired at either 1–5 or 30 s delays. It is suggested that PCP through its blocking action of the NMDA receptor mediates long- but not short-term memory for spatial location information as well as the ability to retrieve previously learned spatial location information.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02257411
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    Environmental and pharmacological sensitization: effects of repeated administration of systemic or intra-nucleus accumbens cocaine (1993)
    Springer
    Psychopharmacology 111 (1993), S. 109-116 
    Details
    ISSN: 1432-2072
    Keywords: Cocaine ; Nucleus accumbens ; Sensitization ; Locomotor activity ; Conditioning ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of repeated systemic or intra-nucleus accumbens cocaine administration on locomotor activity were examined for environmental dependence. Repeated IP administration of cocaine (15 mg/kg) for 5 days in the context of a given environment increased the locomotor response to a subsequent IP cocaine challenge in that environment. However, there were no differences in the locomotor response to a subsequent IP cocaine challenge in the test chamber in subjects which had received prior repeated IP administration of cocaine in the home-cage. In a second experiment, cocaine (100 µg/side) was infused into the nucleus accumbens (NACC) daily for 5 days. This repeated administration produced increases in locomotor activity to subsequent intra-NACC cocaine infusions that were environmentally independent. In contrast to the effects of repeated IP cocaine administration, subjects which received administration of vehicle, acute cocaine, or repeated cocaine in the NACC did not differ following an IP cocaine challenge. The results from these experiments indicate that increases in the response to IP cocaine following repeated IP administration are in part environmentally dependent. Moreover, repeated intra-NACC cocaine infusions increase the responsiveness of the NACC to subsequent intra-NACC cocaine. However, local activation of the NACC alone does not appear to be adequate to produce sensitization to systemically administered cocaine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02257416
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    Differential modification of the rewarding effects of methamphetamine and cocaine by opioids and antihistamines (1993)
    Springer
    Psychopharmacology 111 (1993), S. 139-143 
    Details
    ISSN: 1432-2072
    Keywords: Methamphetamine ; Cocaine ; Opioids ; Antihistamines ; Place preference ; Drug interaction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We previously reported that the reinforcing effects of opioids are enhanced in combination with antihistamines. In the present study, effects of opioids and antihistamines on the reinforcing effects of psychostimulants such as methamphetamine and cocaine were investigated by utilizing the conditioned place preference procedure in rats. The place preference induced by methamphetamine was enhanced in combination with either morphine or chlorpheniramine, which produced additive and potentiative effects, respectively. In contrast, although the preference for cocaine was also enhanced by combination with these two drugs, morphine caused a potentiative effect and chlorpheniramine an additive one. In other words, the reinforcing effect of methamphetamine was differentially enhanced by opioids and antihistamines as compared to that of cocaine. These results suggest that the mechanism of reinforcing effect of methamphetamine is different from that of cocaine, resembling rather those of opioids.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245515
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    Adenosine A2 receptor regulation of apomorphine-induced turning in rats with unilateral striatal dopamine denervation (1993)
    Springer
    Psychopharmacology 111 (1993), S. 383-388 
    Details
    ISSN: 1432-2072
    Keywords: Adenosine A2 receptor ; Apomorphine ; Dopamine-denervation ; Striatum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The ipsilateral intrastriatal administration of the specific adenosine A2a receptor agonist, 2-[p-(2-carboxyethyl)phenethylamino]-5′-N-ethylcarboxamido adenosine (CGS 21680), produced a dose related decrease in apomorphine-induced rotation in the unilaterally 6-hydroxydopamine-lesioned rat. This effect could be reversed by intrastriatal infusions of the A2a antagonist, 4-amino-l-phenyl[1,2,4]triazolo[4,3-a]quinoxaline (CP 66,713). However, CP 66,713 had no significant effect when infused alone, neither did it influence the response to apomorphine in the absence of CGS 21680. The possible behavioural interactions between A2a receptors and striatal ACh activity were also investigated using this model. Atropine administered intrastriatally in a dose that had no effect on the response to apomorphine reduced the inhibitory effects of CGS 21680 on apomorphine-induced turning. Naloxone also reduced the effects of apomorphine, an effect which could be prevented by the co-administration of atropine, or CP 66,713. These results indicate that adenosine agonists can modulate apomorphine-induced turning by an interaction with both cholinergic and opioidergic mechanisms in the striatum.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244956
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  • 133
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    Effects of dopamine D1 and D2 receptor blockade on MK-801-induced hyperlocomotion in rats (1993)
    Springer
    Psychopharmacology 111 (1993), S. 427-434 
    Details
    ISSN: 1432-2072
    Keywords: NMDA antagonist ; MK-801 ; D1/D2 dopamine receptors ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Blocking glutamatergic transmission at the N-methyl-d-aspartate (NMDA) receptor complex with MK-801 (0.15–0.5 mg/kg, IP) was found to induce a robust, dose-dependent increase in locomotor activity. This behavioural activation was similar in intensity to that observed afterd-amphetamine (1 mg/kg, SC). The locomotor stimulation induced by MK-801 at 0.3 mg/kg was significantly inhibited by the D2 dopamine receptor antagonist raclopride (0.1–0.3 mg/kg, SC) and by the D1 receptor antagonist SCH 23390 (0.04 mg/kg, SC). The locomotor activity induced by a higher dose of MK-801 (0.5 mg/kg) was reduced by higher doses of raclopride or SCH 23390 administered alone (0.3 and 0.08 mg/kg, respectively), and was inhibited by simultaneous administration of ineffective doses. Raclopride significantly reducedd-amphetamine-induced locomotor activity at a dose (0.2 mg/kg) that also blocked the effects of a low dose of MK-801. In contrast, SCH 23390 blocked the effects ofd-amphetamine at a dose (i.e. 0.01 mg/kg) lower than that needed to block MK-801. These results suggest that the dopaminergic system may in part mediate the locomotor effects induced by the NMDA antagonist, MK-801, in rats. However, the locomotor activity induced by MK-801 appears to be less sensitive to dopaminergic receptor blockade than that induced byd-amphetamine, suggesting that the underlying mechanisms, although similar, are not identical.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02253532
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  • 134
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    Contrasting effects of the competitive NMDA antagonist CPP and the non-competitive NMDA antagonist MK 801 on performance of an operant delayed matching to position task in rats (1993)
    Springer
    Psychopharmacology 111 (1993), S. 465-471 
    Details
    ISSN: 1432-2072
    Keywords: Delayed matching to position ; Competitive NMDA antagonist ; Non-competitive NMDA antagonist ; Short term memory ; MK 801 ; CPP ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of the competitive NMDA antagonist CPP and the non-competitive NMDA antagonist MK 801 (dizolcipine) on short term working memory in the rat were investigated. The behavioural paradigm used was discrete trial, operant delayed matching to position, as originally described by Dunnett (1985), with delays of 0, 5, 15 and 30 s. These delays generated an orderly “forgetting” curve in control rats, with matching accuracy decreasing from approximately 100% at 0-s delay to approximately 75% at 30-s delay. Intraperitoneal (IP) administration of CPP (10 mg/kg) produced a markeddelay dependent impairment in performance, suggesting a specific effect on short term working memory. This effect was accompanied by a minor decrease in the speed of responding, and a slight increase in the number of missed trials. Lower doses of CPP had no significant effects on either matching accuracy or sedation. In contrast, IP administration of MK 801 (0.1 and 0.2 mg/kg) caused a markeddelay independent impairment in the accuracy of delayed matching performance, suggesting a non-specific disruption of performance. A lower dose (0.05 mg/kg) of MK 801 had no significant effect on matching accuracy. The two lower doses of MK 801 increased the number of nose pokes made during the delays and tended to increase the speed of responding, suggesting a stimulant-like action. The highest dose of MK 801 had the opposite effects and also decreased the number of trials completed. The results with CPP therefore support the hypothesized role of NMDA receptors in learning and memory, and the contrasting effects of these two NMDA antagonists support previous suggestions of different behavioural effects resulting from administration of competitive and non-competitive NMDA antagonists.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02253537
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  • 135
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    Seizure threshold to lidocaine is decreased following repeated ECS (electroconvulsive shock) (1993)
    Springer
    Psychopharmacology 111 (1993), S. 495-498 
    Details
    ISSN: 1432-2072
    Keywords: Seizure threshold ; Electroconvulsive shock ; ECS ; Lidocaine ; GABA-ergic system ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Seizure susceptibility to lidocaine was investigated in rats which had received repeated ECS (electroconvulsive shock). In the first experiment three groups of rats received an ECS daily for 18 days, an ECS weekly for 18 weeks, and 18 sham treatments, respectively. Twelve weeks after the last ECS all rats received a lidocaine challenge (LC) in the form of an intraperitoneal (IP) injection of lidocaine (65 mg/kg). After the injection the animals were observed for occurrence of motor seizures. A total of 67% (10/15), 47% (7/15), and 0% (0/18) of the daily, weekly, and sham groups, respectively, had motor seizures in response to the LC. In the second experiment five groups of rats received an ECS daily for 0, 1, 6, 18, and 36 days, respectively. Eighteen weeks after the last ECS all rats received an LC and 0% (0/15), 13% (2/15), 20% (3/15), 53% (8/15), and 58% (7/12), respectively, developed seizures in response to the LC. In the third experiment two groups of rats received daily ECS and sham-ECS, respectively. Twenty-four hours after the last ECS all rats received an LC. A total of 60% (9/15) of the ECS group and 0% (0/10) of the sham-ECS group had seizures in response to the LC. The study demonstrates a decrease in seizure threshold to lidocaine in ECS-pretreated rats as early as 1 day and as late as 18 weeks following the last ECS, and a positive correlation between the number of ECS administered and the proportion of animals having seizures in response to the LC was found. The convulsant effect of lidocaine has been proposed to be mediated through binding on the GABA receptor-ionophore complex. Therefore this study suggests that ECS causes long-lasting, possibly permanent, changes within the GABA-ergic system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02253542
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  • 136
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    Does the effect of central 5-hydroxytryptamine depletion on timing depend on motivational change? (1993)
    Springer
    Psychopharmacology 112 (1993), S. 86-92 
    Details
    ISSN: 1432-2072
    Keywords: 5-Hydroxytryptamine ; Lesion ; Operant behaviour ; Temporal differentiation ; IRT〉t schedule ; Deprivation level ; Reinforcer magnitude ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a previous experiment we found that destruction of the ascending 5-hydroxytryptaminergic (5HTergic) pathways by microinjection of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei resulted in impaired acquisition of temporal differentiation under an interresponse-time-greater-than-15-s (IRT〉15 s) schedule of sucrose reinforcement. This paper reports three experiments, the results of which bear on the interpretation of that finding. In Experiment 1, 32 rats were trained for 120 sessions under the IRT〉15 s schedule; then 16 received lesions of the 5HTergic pathways and 16 received sham lesions. Comparisons of the IRT frequency distributions of the two groups showed that the lesion produced a significant reduction of the mean IRT and an increase in the dispersion of IRTs, as expressed by the coefficient of variation. Obtained reinforcement rates were significantly reduced in the lesioned group, but response rates were not significantly altered. Levels of 5HT and 5-hydroxyindoleacetic acid were markedly reduced in all forebrain areas examined, without significant change in noradrenaline and dopamine levels. The results indicate that destruction of the 5HTergic pathways disrupts performance as well as acquisition of temporal differentiation. Experiments 2 and 3 examined whether changes in deprivation level and reinforcer magnitude, which are known to affect reinforcer value, would influence temporal differentiation in a similar fashion to destruction of the 5HTergic pathways. In experiment 2, 20 rats were trained under the IRT〉15 s schedule while maintained at 80% or 90% of free-feeding body weight; the more severe deprivation condition was associated with alonger mean IRT and alower coefficient of variation. In experiment 3, 16 rats were trained under the IRT〉15 s schedule using 100 µl or 20 µl of a 0.6 M sucrose solution as the reinforcer; indices of temporal differentiation did not differ between the two conditions. These results indicate that the deleterious effect of destruction of the 5HTergic pathways upon timing behaviour is unlikely to be secondary to the motivation enhancing effect of the lesion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02247367
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  • 137
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    Raclopride, but not SCH 23390, induces maldirected jumping in rats trained to perform a run-climb-run behavioral task (1993)
    Springer
    Psychopharmacology 112 (1993), S. 518-520 
    Details
    ISSN: 1432-2072
    Keywords: Dopamine receptors ; Neuroleptics ; SCH 23 390 ; Raclopride ; Jumping ; Learned behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to explore further the putative differential behavioral consequences of D1 dopamine and D2 dopamine receptor antagonism, SCH 23 390 (0.01–0.12 mg/kg) and raclopride (0.12–1.0 mg/kg) were administered to two separate groups of rats that had been trained in an eight-trial-per-day format to run down an alleyway, climb a vertical rope, and run across a horizontal board to access sweetened milk. Although both drugs dose-dependently reduced the speed of task completion, only raclopride produced vigorous, maldirected jumping behavior in the floor segment of the apparatus. The number of such jumps increased with dose. This raclopride-specific jumping phenomenon may provide a new behavioral arena for investigating the functional differences between D1 and D2 receptor antagonism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244903
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  • 138
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    Quantitative assessment of the microstructure of rat behavior: II. Distinctive effects of dopamine releasers and uptake inhibitors (1993)
    Springer
    Psychopharmacology 113 (1993), S. 187-198 
    Details
    ISSN: 1432-2072
    Keywords: Rat ; Behavior ; Microstructure ; Dopamine releasers ; Dopamine uptake inhibitors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of four indirect dopamine agonists,d-amphetamine (0.25–4.0 mg/kg), cocaine (2.5–40.0 mg/kg), GBR 12909 (10.0–30.0 mg/kg), and nomifensine (5.0–20.0 mg/kg), on the behavioral organization of movements in an unconditioned motor paradigm were investigated in rats. The extended scaling hypothesis using the fluctuation spectrum of local spatial scaling exponents was used to quantify the geometrical characteristics of movements. The results reveal a qualitatively similar disruption of behavioral organization by lower doses of these drugs. Specifically, rats treated withd-amphetamine (〈2.0 mg/kg), cocaine (〈20.0 mg/kg), GBR 12909 (〈20.0 mg/kg), or nomifensine (〈10.0 mg/kg) exhibited a reduced range in the fluctuation spectrum, reflecting a predominance of meandering movements with local spatial scaling exponents between 1.3 and 1.7. This reduction was accompanied dynamically by a reduced predictability of movement sequences as measured by the dynamical entropy,h. By contrast, higher doses of these drugs produced distinctly different changes in behavioral organization. In particular, 4.0 mg/kgd-amphetamine and 40.0 mg/kg cocaine increased the fluctuation range, reflecting relative increases in both straight and circumscribed movements that are interpreted as a combination of spatially extended and local perseveration. In contrast, high doses of 30.0 mg/kg GBR 12909 and 20.0 mg/kg nomifensine induced only local perseveration. High doses ofd-amphetamine, cocaine, GBR 12909 and nomifensine reduced the dynamical entropy,h, indicating an increased predictability of the movement sequences. These results suggest that the generic behavioral change induced by low doses of dopamine agonists is characterized by a reduced variety of path patterns coupled with an increased variability in sequential movement sequences. The differential effects of higher doses of these drugs may be due to their influences on other neurotransmitter systems or differential affinities for different dopamine subsystems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245696
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  • 139
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    Morphine acts in the parabrachial nucleus, a pontine viscerosensory relay, to produce discriminative stimulus effects (1993)
    Springer
    Psychopharmacology 110 (1993), S. 76-84 
    Details
    ISSN: 1432-2072
    Keywords: Opiates ; Discrimination learning ; Conditioned taste aversion ; Parabrachial nucleus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Morphine is known to act centrally to produce discriminative stimulus effects, but the specific neuroanatomical sites mediating this action have not been identified. We used morphine as a discriminative stimulus in a taste aversion paradigm to elucidate the neural basis of morphine's cueing properties. Rats were injected subcutaneously with 5 mg/kg morphine 15 min prior to the presentation of a 0.1% saccharin solution. After 20 min of exposure to the flavor, lithium chloride (130 mg/kg, IP) was injected. On alternate days, an injection of 0.9% physiological saline both preceded and followed the presentation of saccharin. Animals learned to consume significantly less saccharin after morphine than after saline injections. Unilateral guide cannulae were then implanted into brain areas containing relatively high densities of opiate binding sites, comprising the medial prefrontal cortex, the nucleus accumbens, the anterior dorsolateral striatum, the medial thalamus, the basolateral amygdaloid nucleus, the dorsal hippocampus, the caudal periaqueductal grey and the parabrachial nucleus. Generalization to central routes of administration was then evaluated by microinjecting morphine (2.5, 5, 10 and 20 µg) into these brain areas. Dose-dependent decreases in saccharin consumption similar to those of systemic morphine were produced by the administration of morphine into the parabrachial nucleus and the nucleus accumbens. Control data showed that only in the parabrachial nucleus could these effects be attributed to the cueing properties of morphine; in the nucleus accumbens, morphine administration induced unconditioned decreases in saccharin consumption. In the remaining brain areas, morphine generalized to the systemic saline condition. The data point to ascending visceral pathways (parabrachial nucleus), but not dopamine terminal fields (nucleus accumbens), as possible substrates for opiate discriminative effects. These putative discriminative substrates are distinct from the medial forebrain bundle pathways mediating the positive reinforcing effects of opiates.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246953
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  • 140
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    Effect of lesions of the ascending 5-hydroxytryptaminergic pathways on timing behaviour investigated with an interval bisection task (1993)
    Springer
    Psychopharmacology 112 (1993), S. 80-85 
    Details
    ISSN: 1432-2072
    Keywords: 5-Hydroxytryptamine ; 5,7-Dihydroxytryptamine ; Operant behaviour ; Timing ; Intervalbisection procedure ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Seventeen rats received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei: 12 rats received sham injections. The rats were trained in a series of discrete trials to press lever A following a 2-s presentation of a light stimulus and to press lever B following an 8-s presentation of the same stimulus. Both groups learnt the task rapidly and maintained 〉90% accuracy throughout the experiment. When stable performance had been attained, “probe” trials were introduced in which the light was presented for intermediate durations. Both groups showed sigmoid functions relating percent choice of lever B to log stimulus duration. The bisection point (duration corresponding to 50% choice of lever B) was significantly shorter in the lesioned group than in the control group. There was no significant difference between the slopes of the psychophysical functions or the Weber fractions derived for the two groups. The levels of 5-hydroxytryptamine (5HT) and 5-hydroxyindoleacetic acid in the parietal cortex, hippocampus, amygdala, nucleus accumbens and hypothalamus were markedly reduced in the lesioned group, but the levels of noradrenaline and dopamine were not significantly affected by the lesion. The results confirm the involvement of 5HTergic function in timing behaviour, but suggest that destruction of these pathways does not disrupt the capacity for temporal discrimination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02247366
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    Effect of 5-HT3 receptor antagonists on the discriminative stimulus properties of morphine in rats (1993)
    Springer
    Psychopharmacology 112 (1993), S. 111-115 
    Details
    ISSN: 1432-2072
    Keywords: Morphine drug discrimination ; Rat ; 5-HT3 receptor antagonists ; Opioid ; Naloxone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 5-HT3 receptor antagonists, e.g. MDL72222, ondansetron and ICS205-930, have been previously reported to block a morphine (1.5 mg/kg)-induced conditioned place preference in rats. This finding suggests that these drugs may modify the morphine discriminative stimulus which underlies place conditioning. To study this further we have examined the effects of MDL72222, ondansetron and ICS205-930 against a morphine discriminative stimulus using a two-choice, food reinforced, operant paradigm. In an attempt to provide consistency with previous place conditioning studies, a morphine training dose of 1.5 mg/kg was used in addition to a higher 3 mg/kg dose which was studied in separate animals. Stimulus control of behaviour was attained at both morphine training doses, the characteristics of each being consistent with an effect at the mu opioid receptor. Ondansetron (0.001–1 mg/kg), MDL72222 (0.1–3 mg/kg), and ICS205-930 (0.001–1 mg/kg) all failed to consistently antagonise the morphine cue at both training doses, although a mild attenuation was seen in the 1.5 mg/kg group following pretreatment with an intermediate dose of ondansetron and ICS205-930 (both 0.01 mg/kg). The present results therefore suggest hat 5-HT3 antagonists do not block a morphine discriminative state, at least in rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02247370
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    Sequence-specific effects of neurokinin substance P on memory, reinforcement, and brain dopamine activity (1993)
    Springer
    Psychopharmacology 112 (1993), S. 147-162 
    Details
    ISSN: 1432-2072
    Keywords: Peptides ; Tachykinins ; Substance P fragments ; Inhibitory avoidance learning ; Conditioned place preference ; Nucleus basalis magnocellularis ; Dopamine ; Neostriatum ; Nucleus accumbens ; In vivo microdialysis ; Neurodegeneration ; Alzheimer's disease ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There is ample evidence that the neurokinin substance P (SP) can have neurotrophic as well as memory-promoting effects. This paper outlines a recent series of experiments dealing with the effects of SP and its N- and C-terminal fragments on memory, reinforcement, and brain monoamine metabolism. It was shown that SP, when applied peripherally (IP), promotes memory (inhibitory avoidance learning) and is reinforcing (place preference task) at the same dose of 37 nmol/kg. Most important, however, is the finding that these effects seemed to be encoded by different SP sequences, since the N-terminal SP1-7 (185 nmol/kg) enhanced memory, whereas C-terminal hepta- and hexapeptide sequences of SP proved to be reinforcing in a dose equimolar to SP. These differential behavioral effects were paralleled by selective and site-specific changes in dopamine (DA) activity, as both SP and its C-, but not N-terminus, increased extracellular DA in the nucleus accumbens (NAc), but not in the neostriatum. The neurochemical changes lasted at least 2 h after injection. These results show that the reinforcing action of peripheral administered SP may be mediated by its C-terminal sequence, and that this effect could be related to DA activity in the NAc. Direct application of SP (0.74 pmol) into the region of the nucleus basalis magnocellularis (NBM) was also memory-promoting and reinforcing, and again, these effects were differentially produced by the N-terminus and C-terminus, supporting the proposed structure-activity relationship for SP's effects on memory and reinforcement. These results may provide a hypothetical link between the memory-modulating and reinforcing effects of SP and the impairment in associative functioning accompanying certain neurodegenerative processes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244906
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    Differences in morphine reinforcement property in two inbred rat strains: associations with cortical receptors, behavioral activity, analgesia and the cataleptic effects of morphine (1993)
    Springer
    Psychopharmacology 112 (1993), S. 183-188 
    Details
    ISSN: 1432-2072
    Keywords: Morphine ; Behavioral activity ; Analgesia ; Rat ; Self-administration ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of the current study was to investigate genetic differences between two inbred strains of rats, Fisher-344 (F344/N) and Wistar Albino Glaxo (WAG/GSto), in a number of drug-naive and drug-related behaviors, including oral and intravenous morphine self-administration. F344/N and WAG/GSto rats differed in drug-naive behaviors such as nociception, rearing and sensitivity to lick suppression tests but did not differ in locomotor activity, ambulation or grooming behavior. F344/N rats were less sensitive to thermal stimuli as measured via tail-flick response, and more sensitive to the suppressive effects of intermittent shock in a lick suppression test. The F344/N rats demonstrated a significantly greater amount of rearing in open field tests but did not differ from WAG/GSto rats in locomotor activity, ambulation or grooming behavior. In addition to the behavioral results, naive F344/N and WAG/GSto rats were found to differ in μ and α2 receptor concentrations (F344/N〉WAG/GSto) and in 5HT2 and D2 affinity constants (WAG/GSto〉F344/N). These two inbred rat strains also differed in drug-related behaviors. F344/N rats showed significantly greater depression of locomotor activity at morphine 3 mg/kg than WAG/GSto rats. In addition, F344/N rats consumed significantly greater amounts of morphine in a two-bottle choice procedure and morphine maintained significantly greater amounts of behavior during intravenous self-administration sessions. Importantly, drug maintained behavior was significantly greater than with vehicle only in the F344/N rats during operant self-administration sessions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244908
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    Individual differences in the feeding effects of amphetamine: role of nucleus accumbens dopamine and circadian factors (1993)
    Springer
    Psychopharmacology 112 (1993), S. 211-218 
    Details
    ISSN: 1432-2072
    Keywords: Amphetamine ; cis-Flupenthixol ; Nucleus accumbens ; Feeding ; Sugar ; Baseline dependent ; Circadian ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Evidence indicates that amphetamine (AMP) affects feeding in a baseline-dependent fashion and that the nucleus accumbens (Acc) is an important site of action for AMP's effects on feeding. Experiment 1 examined the contribution of Acc-dopamine (DA) mechanisms to the baseline-dependent feeding effects of a 0.125 mg/kg dose of AMP using intra-Acc administrations of cis-flupenthixol (FLU). Results showed that there was an inverse relation beetween baseline sugar intake and the feeding response to AMP, such that AMP stimulated feeding in animals with low baseline intake and inhibited feeding in animals with high baseline intake. Intra-Acc FLU administration reversed the stimulatory but not the inhibitory effect of AMP. Further, intra-Acc FLU attenuated baseline feeding in high but not low baseline feeders. Experiment 2 sought to determine whether AMP would affect feeding in a baseline-dependent manner when administered in the dark photoperiod of the rat circadian cycle, when rats do most of their feeding. To this end, rats were administered three doses (0.05, 0.1, and 0.25 mg/kg) of AMP in the dark photoperiod and the intake of sugar monitored. Results showed that in low baseline feeders, AMP stimulated intake at lowest dose and had no effect at higher doses. In high baseline feeders, AMP inhibited intake in a dose-dependent manner. Taken together, these results further establish that AMP affects feeding in a baseline-dependent fashion. Moreover, the similar effects of AMP across the light and dark photoperiods suggest that a straightforward rate-dependency interpretation is not adequate. Finally, it is speculated that Acc-DAergic activity may play a role in the observed differences in baseline intake levels and in the response to AMP.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244913
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    Anatomical differentiation within the nucleus accumbens of the locomotor stimulatory actions of selective dopamine agonists andd-amphetamine (1993)
    Springer
    Psychopharmacology 112 (1993), S. 233-241 
    Details
    ISSN: 1432-2072
    Keywords: Dopamine ; SKF 38393 ; Quinpirole ; d-Amphetamine ; Nucleus accumbens ; Localization ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of local injections of dopamine receptor agonists into various areas within the nucleus accumbens or the medial caudate-putamen on the generation of locomotor activity were examined. Combinations of 0.32 µg/side of the dopamine receptor agonists SKF 38393 (D1) and quinpirole (D2) produced increases in locomotor activity that varied according to the rostral-caudal placement of the cannulae within the nucleus accumbens. The greatest levels of locomotion were generated by injections into a region in the caudal-central nucleus accumbens, with lower levels of activity elicited by injections into more rostral or caudal regions. A similar pattern of responses was produced by administration of the indirect dopamine agonistd-amphetamine. These results indicate that there is marked heterogeneity in the response of discrete sub-regions of the nucleus accumbens to dopamine receptor stimulation and that this heterogeneity is functionally expressed in the mediation of the locomotor effects of dopaminergic agonists.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244916
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    Beta adrenergic and muscarinic receptors in compensatory cardiac hypertrophy of the adult rat (1993)
    Springer
    Pflügers Archiv 424 (1993), S. 354-360 
    Details
    ISSN: 1432-2013
    Keywords: β-Adrenergic receptors ; Muscarinic receptors ; Cardiac hypertrophy ; Cardiac myocyte ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The beta adrenergic (βAR) and muscarinic (MR) receptors have been quantitated in parallel, using 125I-pindolol and 3H-quinuclidinylbenzilate, in a model of compensatory left ventricular (LV) hypertrophy (LVH), which developed in rats 4–6 weeks after an abdominal aortic stenosis. Since aortic banding resulted in a pronounced LVH of 62%, the results were expressed both in terms of density (fmol/mg protein) and quantity (fmol per LV). In addition, competition curves using either a specific β1-antagonist or isoproterenol or carbachol allowed the determination of the two βAR subtypes and of the low and high affinity sites (defined by the inhibitory constant K i) for both β1AR and MR. In LVH, receptor density decreased for each of total βAR, β1AR subtype, high affinity (K i 6–8nM) β1AR sites (from 26±2 to 19±3 fmol/mg protein, P〈0.05), total MR and high affinity (K i 12 nM) MR sites (from 63±6 to 40±4 fmol/mg protein, P〈0.001). The βAR and MR densities dropped in parallel so that the MR/βAR ratio remained unchanged. In sharp contrast (because the LVs were bigger) the quantities of total βAR, β1 AR subtype, β1AR high affinity sites, total MR and MR high affinity sites per LV were unmodified. Thus, in compensatory LVH the total quantity of receptors per LV was unchanged, suggesting that either both synthesis and degradation were augmented in parallel or that during the process of cardiac hypertrophy they are not regulated, i. e., that the genes encoding for the two receptors were not activated, as it has been suggested for other membrane proteins. Assuming that the high affinity sites represent the receptors coupled to the adenylyl cyclase, we also propose that the overall regulatory systems were modified beyond the level of the receptors.
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    URL: http://dx.doi.org/10.1007/BF00384363
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    Oxygen-dependent expression of the erythropoietin gene in rat hepatocytes in vitro (1993)
    Springer
    Pflügers Archiv 423 (1993), S. 356-364 
    Details
    ISSN: 1432-2013
    Keywords: Erythropoietin ; Hepatocytes ; Rat ; In vitro ; Hypoxia ; Signalling ; mRNA ; RNase protection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Since in juvenile rats the liver is the predominant site of erythropoietin (EPO) gene expression, we have used primary cultures of juvenile rat hepatocytes to establish an in vitro system for investigation of oxygen-dependent EPO formation. When isolated hepatocytes were incubated at reduced oxygen tensions for 18–48 h, we found increased secretion of EPO protein and elevated levels of EPO mRNA, as determined by RNase protection. This increase was maximal at 3% O2, where EPO mRNA levels after 18 h were approximately 15fold higher than at 20% O2. The increase in EPO mRNA at low oxygen tensions was specific insofar as [3H]uridine incorporation, as a measure of total RNA synthesis, was reduced by approximately 50% at 3% O2, and it appeared to involve gene transcription since it was abolished in the presence of actinomycin D (35 μM). Significant increases in EPO mRNA were also observed in cells kept at 20% oxygen in the presence of cobalt chloride (50 μM) and nickel chloride (400 μM), but EPO mRNA levels achieved under these conditions were less than 7% of those in cells incubated at 3% oxygen. No increase in EPO mRNA levels was observed in cultures incubated at 20% O2 in the presence of cyclic dibutyrylAMP (10 μM-3 mM), cyclic 8-bromoGMP (10 μM1 mM), cyclohexyladenosine (1 μM), 5′-N-ethylcarboxamidoadenosine (1 μM) and phorbol 12-myristate 13acetate (3 nM). In the presence of 10% carbon monoxide, used to block haem proteins in their oxy conformation, EPO mRNA levels in hepatocytes incubated at low oxygen tensions were reduced to 63%. Taken together, these findings indicate that oxygen-dependent control of the EPO gene in hepatocytes operates via intrinsic cellular oxygen-sensing mechanisms. Their signal transduction does not seem to occur via classical “second-messenger” pathways. A haem protein may be involved in oxygen sensing, but no conclusive evidence was obtained as to whether it is essential.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00374928
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  • 148
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    Renal and single-nephron function is comparable in thiobutabarbitone- and thiopentone-anaesthetised rats (1993)
    Springer
    Pflügers Archiv 424 (1993), S. 224-230 
    Details
    ISSN: 1432-2013
    Keywords: Rat ; Renal function ; Micropuncture ; Blood gases ; Anaesthesia ; Thiopentone ; Thiobutabarbitone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The thiobutabarbitone(TB, Inactin)-anaesthetised rat is an extremely widely used preparation for the study of renal function at the whole-organ and nephron levels. The recent withdrawal of TB from the market has made it essential to find an anaesthetic producing experimental conditions as similar as possible to TB to allow comparison of past and future data. Blood gas analysis, clearance and micropuncture studies were therefore performed in rats anaesthetised with TB or the related thiobarbiturate thiopentone (TP) (both 100 mg/ kg body weight) to establish whether the latter meets this requirement. Both barbiturates caused similar transient respiratory depression and acidosis. Mean values (TP versus TB) over the total 8-h observation period for glomerular filtration rate (0.94 versus 1.05 ml/min), urine flow (3.8 versus 4.4 μl/min) and K+ excretion (0.98 versus 1.18 μmol/min) were slightly lower (P〈0.05) in TP rats, whereas renal blood flow (6.26 versus 6.24 ml/min), filtration fraction (0.31 versus 0.34) and Na+ excretion (0.11 versus 0.098 μmol/min) did not differ. The single-nephron filtration rate (SNGFR) (42.1 versus 41.1 nl/min) and fractional reabsorption (42% versus 47%), both measured in the proximal tubule, did not differ, although in the TP group SNGFR rose with time (4.4%/h) whereas the fractional reabsorption did not change significantly; in the TB group SNGFR was constant but fractional reabsorption declined with time (1.5%/h). Fractional reabsorption up to the distal convoluted tubule declined with time, this was more pronounced in the TP group. SNGFR measured at this site did not differ between TP and TB (30.3 versus 30.1 nl/min) but increased with time with TP (2.7%/h). Although renal function under TP is somewhat less stable than under TB, the differences are minor and, given that the latter is also characterised by non-steady-state conditions, it is concluded that TP is a reasonable replacement for TB.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00384346
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  • 149
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    Modulation of sarcoplasmic reticulum Ca2+-release channels by caffeine, Ca2+, and Mg2+ in skinned myocardial fibers of fetal and adult rats (1993)
    Springer
    Pflügers Archiv 423 (1993), S. 300-306 
    Details
    ISSN: 1432-2013
    Keywords: Ryanodine ; Rat ; Fetus ; Adult ; Skinned myocardial fibers ; Caffeine ; Calcium ; Magnesium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ryanodine causes depression of the caffeine-induced tension transient (ryanodine depression) in skinned muscle fibers, because it blocks the sarcoplasmic reticulum (SR) Ca2+-release channels [Su, J. Y. (1988) Pflügers Arch 411:132–136, 371–377; (1992) Pflügers Arch 421:1–6]. This study was performed to examine the sensitivity of SR Ca2+-release channels to ryanodine in fetal compared to adult myocardium and to investigate the influence of Ca2+, caffeine, and Mg2+ on ryanodine depression in skinned fibers. Ryanodine (0.3 nM–1 μM) caused a dose-dependent depression in skinned myocardial fibers of the rat, and the fetal fibers (IC50≈74 nM) were 26-fold less sensitive than those of the adult (IC50≈2.9 nM). The depression induced by 0.1 μM or 1 μM ryanodine was a function of [caffeine], or [Ca2+] (pCa〈6.0), which was potentiated by caffeine, and an inverse function of [Mg2+]. At pCa〉8.0 plus 25 mM caffeine, a 20% ryanodine depression was observed in both the fetal and adult fibers, indicating independence from Ca2+. Ryanodine depression in skinned fibers of the fetus was less affected than that seen in the adult by pCai, [caffeine]i, or 25 mM caffeine plus pCai or plus pMgi (IC50≈pCa 4.5 versus 5.1; caffeine 12.7 mM versus 2 mM; pCa 6.7 versus 7.3; and pMg 3.9 versus 3.3 respectively). The results show that the SR Ca2+-release channel in both fetal and adult myocardium is modulated by Ca2+, caffeine, and Mg2+. It is concluded that less ryanodine depression seen in the skinned fibers of the fetus, indicating a relatively insensitive SR Ca2+-release channel, could contribute to the resistance of intact myocardium to ryanodine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00374409
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  • 150
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    Effects of antipsychotic drugs on latent inhibition: sensitivity and specificity of an animal behavioral model of clinical drug action (1993)
    Springer
    Psychopharmacology 112 (1993), S. 315-323 
    Details
    ISSN: 1432-2072
    Keywords: Animal model ; Rat ; Antipsychotic ; Schizophrenia ; Latent inhibition ; Attention ; Selective attention ; Conditioned emotional response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Latent inhibition (LI) of a conditioned emotional response (CER) has been proposed as a quantitative measure of selective attention. We have assessed the parallels of the pharmacology of LI in rats with the clinical pharmacology of schizophrenia. Drug and vehicle treated rats were divided into groups and preexposed 20 times to cage illumination as a CS, or not preexposed. All groups were conditioned with 2 CS-footshock pairings. The following day CER, as measured by interruption of drinking in response to CS presentation, was recorded. LI was observed as a decreased CER in preexposed relative to non-preexposed animals. LI was enhanced by haloperidol 0.3 mg/kg after 7 or 14 daily treatments, but not after a single acute dose. Haloperidol doses of 0.3 and 0.03 mg/kg enhanced LI, while doses of 0.003 and 3.0 mg/kg had no effect. Haloperidol enhancement of LI was unaffected by the coadministration of the anticholinergic agent trihexyphenidyl. Enhancement of LI is exhibited by the antipsychotic drugs fluphenazine, chlorpromazine, thiothixene, thioridazine, mesoridazine, and metoclopramide but not clozapine. The non-antipsychotic drugs pentobarbital, imipramine, chlordiazepoxide, trihexyphenidyl, and promethazine failed to enhance LI. LI exhibits striking parallels to the clinical pharmacology of schizophrenia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244927
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  • 151
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    Nicotine withdrawal: a behavioral assessment using schedule controlled responding, locomotor activity, and sensorimotor reactivity (1993)
    Springer
    Psychopharmacology 113 (1993), S. 205-210 
    Details
    ISSN: 1432-2072
    Keywords: Nicotine ; Withdrawal ; Discrimination ; Activity ; Startle ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Three different behavioral measures were used to assess the effects of abrupt cessation of chronic nicotine treatment. Nicotine (0, 3, or 6 mg/kg per day) was continuously administered for 12 days in rats by surgically implanting Alzet osmotic mini-pumps subcutaneously. Experiment 1 employed a light/dark discrimination task. There were no significant effects on number of responses or percent correct responding either during nicotine administration, or following cessation of nicotine. Experiment 2 examined ambulatory (locomotor) and nonambulatory activity. Chronic nicotine administration produced significant dose-dependent increases in both ambulatory and nonambulatory activity during the first 3 days of exposure. However, no significant alterations were seen in activity levels following nicotine cessation. Experiment 3 examined sensorimotor reactivity using the auditory startle response. During nicotine withdrawal, significant increases were seen in startle amplitude in both nicotine groups for 4 days. Nicotine (0.4 mg/kg, IP) administered before startle testing during the withdrawal phase attenuated the increased reactivity seen during nicotine cessation. These studies indicate that 1) rats display increased sensorimotor reactivity after cessation of chronic nicotine exposure, and 2) the expression of nicotine dependence and withdrawal is dependent on the behavioral task employed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245698
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  • 152
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    The new potent and selective histamine H2 receptor agonist amthamine as a tool to study gastric secretion (1993)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 348 (1993), S. 77-81 
    Details
    ISSN: 1432-1912
    Keywords: Amthamine ; Histamine H2 receptors ; Gastric acid secretion ; Conscious cat ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The new histamine H2 receptor agonist amthamine, [2-amino-5-(2-aminoethyl)-4-methylthiazole], was tested for its activity on gastric acid secretion in different in vivo and in vitro experimental models. Amthamine induced a dose-related increase in acid secretion both in conscious cats with a gastric fistula (ED50 = 0.069 μmol/kg/h) and in anaesthetized rats with a lumen-perfused stomach (ED50 = 11.69 gmol/kg i.v.). In this last preparation the efficacy of amthamine was significantly higher than that of histamine and dimaprit. Amthamine was an effective secretagogue also in the rat isolated gastric fundus, behaving as a full agonist (EC50 = 18.9 μmol/l). In all the experimental models amthamine was more potent than dimaprit (from 3 to 10 fold) and approximately equipotent with histamine, and its effect was competitively antagonized by the histamine H2 receptor antagonists famotidine or ranitidine. Experiments with H1 and H3 receptor antagonists indicated that Amhamine is devoid of stimulatory activity at H1 and H3 receptors. The present data indicate that amthamine is a full agonist at histamine H2 receptors and, being more effective and selective than the other compounds of the family, it may represent a good alternative to the other available histamine H2 receptor agonists for the study of gastric acid secretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00168540
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  • 153
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    Neurobehavioural effects of SR 27897, a selective cholecystokinin type A (CCK-A) receptor antagonist (1993)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 348 (1993), S. 102-107 
    Details
    ISSN: 1432-1912
    Keywords: CCK-A receptor ; Food intake ; Locomotor activity ; cGMP levels ; Dopaminergic cells ; Rat ; Mouse ; CCK antagonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The activity of SR 27897, a potent and selective CCK-A vs CCK-B receptor antagonist (Ki = 0.2 nM on guinea-pig pancreas vs 2000 nM on rat brain) was studied on behavioural, electrophysiological and biochemical effects induced by peripheral or central injection of CCK-8S. For comparative purposes, devazepide, a reference CCK-A receptor antagonist, was investigated in these same models. CCK-induced hypophagia and CCK-induced hypolocomotion in rats, two behavioural changes associated with the stimulation of peripheral CCK-A receptors, were dose-dependently antagonized by SR 27897 (ED50 = 0.003 and 0.002 mg/kg i.p., respectively) and devazepide (ED50 = 0.02 and 0.1 mg/kg i.p., respectively). CCK-induced decrease of cerebellar cGMP levels in mice was also reduced by SR 27897 (ED50 = 0.013 mg/kg) and by devazepide (0.084 mg/kg). The CCK-induced turning behaviour after intrastriatal injection in mice, and the potentiation of the rate suppressant activity of apomorphine on rat DA neurons, were blocked by higher doses of SR 27897 and devazepide, consistent with the probable central origin of these effects. The respective ED50s were 0.2 mg/kg i.p. for SR 27897 and 4.9 mg/kg i.p. for devazepide in the former model, while the respective minimal effective doses were 1.25 and 5 mg/kg i.p. in the latter test. In most tests the i.p./p.o. ratio for SR 27897 was near unity, suggesting a high oral bioavailability of the compound. Taken together, these findings support the notion that SR 27897 behaves as a potent CCK-A antagonist able to cross the blood brain barrier.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00168544
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  • 154
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    Capsaicin sensitive nerves in the jejunum of Nippostrongylus brasiliensis-sensitized rats participate in a cardiovascular depressor reflex (1993)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 348 (1993), S. 638-642 
    Details
    ISSN: 1432-1912
    Keywords: Guanethidine ; Rat ; Capsaicin ; Primary afferent nerves ; Nippostrongylus brasiliensis ; Ruthenium red
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Superfusion of capsaicin onto the serosal surface of jejunum of Nippostrongylus brasiliensis-sensitized rats induces a short-lasting (1–3 min), dose-dependent (2 to 20 μg) decrease in blood pressure which ranges from −5.3±1.40% to −22.6±2.20%. The hypotension evoked by capsaicin was more marked in sensitized rats than in unsensitized animals, which responded only to the highest dose (20 mg) of capsaicin tested. The hypotensive effects of capsaicin were not affected by intravenous injections of mepyramine (10 mg/kg), a histamine receptor antagonist, or by the cycloxygenase inhibitor indomethacin (10 mg/kg). However, an intravenous injection of a platelet-activating factor (PAT) antagonist, BN 52021 (20 mg/kg), or an intraperitoneal injection of guanethidine (8 mg/kg) 18 h prior to experimentation, to functionally impair the sympathetic nerves, abolished the capsaicin-induced drop in blood pressure. Treatment of neonatal rats with capsaicin reduced by 75% the hypotensive effects of capsaicin, whereas the capsaicin antagonist, ruthenium red, reduced non-significantly the hypotensive action of capsaicin. It is concluded that the activation of jejunal sensory nerves in N. brasiliensis-sensitized rats by capsaicin induced a reflex hypotension that is dependent upon PAF release from mast cells and functional sympathetic nerves. In addition, the afferent function of the sensory nerves are not totally blocked by ruthenium red as capsaicin elicits the reflex hypotension in the presence of this blocker of sensory nerve efferent function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00167241
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  • 155
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    The antagonist actions of WAY 100135 and its enantiomers on 5-HT1A receptor-mediated hyperpolarization of the rat isolated superior cervical ganglion (1993)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 348 (1993), S. 225-227 
    Details
    ISSN: 1432-1912
    Keywords: WAY-100135 ; 5-HT1A receptor antagonists ; Enantiomers ; Rat ; Superior cervical ganglion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A grease-gap extracellular recording technique was used to detect 5-HT1A receptor-mediated hyper-polarizing responses to 5-hydroxytryptamine (5-HT) in the rat isolated superior cervical ganglion. In the presence of the novel 5-HT1A receptor antagonist, WAY 100135 [N-tert-butyl-3-(4-(2-methoxyphenyl)piperazin-1-yl)-2-phenylpropanamide], the responses to 5-HT were antagonised in a competitive manner with a pA2 value of 7.2 (6.9–8.5) and Schild plot slope of 1.0 (0.4–1.6), n = 20. The antagonist activity was greater in the (+) than the (−)enantiomer of WAY-100135. The pA2 value of the (+)enantiomer was 7.5 (7.2–8.0), Schild plot slope 1.2 (0.8–1.6), n = 17. In contrast the (−)enantiomer had weak antagonist activity (pA2 6.3±0.25, n = 3). No agonist activity of WAY-100135 or its enantiomers were observed in this study.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00169148
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  • 156
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    Neurofilaments in rat and cat spinal cord; a comparative immunocytochemical study of phosphorylated and non-phosphorylated subunits (1993)
    Springer
    Cell & tissue research 272 (1993), S. 249-256 
    Details
    ISSN: 1432-0878
    Keywords: Spinal cord ; Motoneurones ; Dorsal horn ; Neurofilament ; Phosphorylation ; Immunocytochemistry ; Rat ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Neurofilament immunoreactivity was examined in spinal cords of rats and cats with antibodies to all three subunits (68 kD, 155 kD and 200 kD) and to different phosphorylation states of 200 kD. NFHP-, an antibody against non-phosphorylated 200 kD, labelled all rat neuronal perikarya but failed to labet cat neurofilaments. In both species, the perikarya and processes of motoneurones were immunoreactive for all three subunits but most dorsal horn neuronal perikarya were not immunoreactive for 68 kD and 155 kD. Motoneuronal perikarya and proximal processes showed filamentous labelling for 68 kD but not for 155 kD in the rat, while in neither species did these show labelling with RT97, an antibody against a highly phosphorylated form of 200 kD; immunoreactivity for 200 kD was present in both filamentous (probably partially phosphorylated) and non-filamentous (non-phosphorylated) forms, but in dorsal horn neurones only the latter was present. Interpretations consistent with this data are: in rat and possibly also cat, motoneuronal neurofilaments consist of a 68 kD backbone with partially phosphorylated 200 kD sidearms, with both 155 kD and 200 kD (non-phosphorylated) subunits in a non-filamentous form; this neurofilament becomes more highly phosphorylated along the proximal processes. The dorsal horn neurones probably contain 200 kD in a non-filamentous form but may lack the other subunits.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00302730
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  • 157
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    Immunohistochemical localization of insulin-like growth factor 1 and 2 in the endocrine pancreas of rat, dog, and man, and their coexistence with classical islet hormones (1993)
    Springer
    Cell & tissue research 273 (1993), S. 249-259 
    Details
    ISSN: 1432-0878
    Keywords: Endocrine pancreas ; IGF-1 ; IGF-2 ; Insulin ; Glucagon ; Somatostatin ; Pancreatic polypeptide ; Man ; Dog ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Immunohistochemical techniques were used to study the occurrence and distribution of insulin-like growth factor 1 (IGF-1) and IGF-2 in the pancreas of man, dog, and rat and their possible coexistence with insulin (INS), glucagon (GLUC), somatostatin (SOM) and pancreatic polypeptide (PP). All control experiments, including pre-absorption of the antisera with synthetic peptide hormones, indicated the specificity of the immunoreactions obtained. In all species investigated, IGF-2-immunoreactivity occurred exclusively in INS-immunoreactive cells as was found by the use of consecutive sections and double immunofluorescence on identical sections. In contrast, IGF-1-immunoreactivity co-existed with GLUC-immunoreactivity. In man, singular SOM-immunoreactive cells also contained IGF-1-immunoreactivity. Thus, IGF-1 and IGF-2 can be localized by means of immunohistochemistry in the mammalian pancreas, and can be shown to occur in different islet cell populations. It is presumed that IGF-1 derived from A-cells and/or D-cells acts on the B-cells in a paracrine manner. The co-existence of IGF-2-immunoreactivity and INS-immunoreactivity in the human, rat, and dog endocrine pancreas indicates that mammalian IGF-2 and INS genes are regulated simultaneously.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00312826
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  • 158
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    Atrial natriuretic peptide binding in rat placenta, yolk sac, decidua, and materal placental vessels (1993)
    Springer
    Cell & tissue research 272 (1993), S. 391-394 
    Details
    ISSN: 1432-0878
    Keywords: ANP binding ; Yolk sac ; Decidua ; Maternal placental vessels ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Using in vitro autoradiography, binding sites of 125I-ANP (atrial natriuretic peptide) were localized in the rat placenta, visceral yolk sac, and decidua at 16, 18, and 20 days of gestation. There was diffuse binding over the labyrinthine region of the placenta and an intense binding over the decidual gland and visceral yolk sac. In the yolk sac, ANP localized over the cores of the villi where it may be involved with the regulation of transport across the membranes or the flow of blood through the vitelline vessels. Of particular interest was binding over the maternal blood vessels supplying the decidual region and placenta. Receptors were located on the endothelial cells and smooth muscle cells of the arteries and veins, indicating that ANP may be involved with regional regulation of blood flow to the placenta.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00302744
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  • 159
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    A monoclonal antibody disrupting cell-cell adhesion of rat ascites hepatoma cells (1993)
    Springer
    Cell & tissue research 273 (1993), S. 363-370 
    Details
    ISSN: 1432-0878
    Keywords: Ascites hepatoma ; Adhesive factor ; Monoclonal antibody ; Cell membrane polarity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract A cell surface-associated adhesive factor (AF) separated from differentiated rat ascites hepatoma AH136B cells (forming cell islands in vivo) has been highly purified by chromatography. AF is assumed to mediate the cell-cell adhesion essential to island formation of the hepatoma cells. A substance, immunologically crossreactive with AF, is present in the ascites fluid or culture medium of the AH136B cells. Because the substance is almost identical to AF in molecular weight and aggregation-promoting activity, it has been concluded that AF is released into the ascites fluid where it is concentrated. Monoclonal antibodies have been raised against AF purified from ascites fluid of AH136B cells. We have obtained a monoclonal antibody, coded MoAF-6D6, that strongly abolishes the aggregation-promoting activity of AF. When AH136B cell islands are incubated in the presence of Fab fragments of MoAF-6D6, cell detachment from the islands is evident within 24 h. Cell islands following 36-h culture show a distinct dissociation and islands completely lose their organization 48 h after culture. The dissociating effect of MoAF-6D6 is neutralized by the addition of AF. These results suggest that AF plays a significant role in the maintenance of cell islands.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00312839
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  • 160
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    Heredity of muscle fibre composition estimated from a selection experiment in rats (1993)
    Springer
    European journal of applied physiology 66 (1993), S. 85-89 
    Details
    ISSN: 1439-6327
    Keywords: Successive selection ; Selection response ; Selection differential ; Realized heritability ; Percentage of slow twitch fibres ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The extent to which muscle fibre composition was determined by the genes transmitted from parents was estimated by using successive selections of rats. A foundation population (GO) was established to carry out the selections; it consisted of 100 albino rats which were randomly chosen from heterogeneous stock. The heterogeneous stock was produced by random-mating of three strains, Wistar-Imamichi, Fischer 344 and Donryu. Successive selection for a high percentage of slow twitch fibres (% ST) was made from GO to the fourth generation (G4). The mean values of % ST changed from 50.0% in G0 to 55.6% in G4. The mean value in G4 was significantly higher than that in GO. The realized heritability in G0–G4 was calculated from the regression of selection response on the cumulated selection differential. The regression coefficient was 0.17 (SEM 0.04). The realized heritability was significantly different from 0 at the 0.05 level. We concluded that in rats about 17% of the variation of muscle fibre composition was determined by the genes transmitted from parents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00863405
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  • 161
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    The effects of a high carbohydrate diet on postprandial energy expenditure during exercise in rats (1993)
    Springer
    European journal of applied physiology 66 (1993), S. 445-450 
    Details
    ISSN: 1439-6327
    Keywords: High-carbohydrate diet ; Oxygen consumption ; Prolonged exercise ; Glycogen ; Liver ; Muscle ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Whether or not a high intake of carbohydrate increases postprandial energy expenditure during exercise was studied in rats. The rats were meal-fed regularly twice a day (0800–0900 hours and 1800–1900 hours) on either a high carbohydrate (CHO) (carbohydrate/fat/protein = 70/5/25, % of energy) or high fat (FAT) (35/40/25) diet for 12 days. On the final day of the experiment, all of the rats in each dietary group were fed an evening meal containing equal amounts of energy (420 kJ · kg−1 body mass). After the meal, they were divided into three subgroups: pre-exercise control (PC), exercise (EX), and resting control (RC). The PC-CHO and PC-FAT groups were sacrificed at 2030 hours. The EX-CHO and EX-FAT groups were given a period of 3-h swimming, and then sacrificed at 2330 hours. The RC-CHO and RC-FAT groups rested after the meal and were sacrificed at 2330 hours. Total energy expenditure during the period 1.5 h from the commencement of exercise was higher in EX-CHO than in EX-FAT. The respiratory exchange ratio was also higher in EX-CHO than in EX-FAT, suggesting enhanced carbohydrate oxidation in the former. Compared with both PC-FAT and RC-FAT, the liver glycogen content of EX-FAT rats was significantly decreased by exercise. On the other hand, the liver glycogen content of both EX-CHO and RC-CHO was higher than that of PC-CHO rats. The glycogen content of soleus muscle of EX-FAT was slightly decreased during exercise, however, that of EX-CHO increased significantly. Thus postprandial energy expenditure during exercise was higher in the rats fed the CHO diet than in those fed the FAT diet, which could have been related to the increase of both liver and muscle glycogen storage during exercise in the former.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00599619
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  • 162
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    Relationship between myosin heavy chain IId isoform and fibre types in soleus muscle of the rat after hindlimb suspension (1993)
    Springer
    European journal of applied physiology 66 (1993), S. 451-454 
    Details
    ISSN: 1439-6327
    Keywords: Hindlimb suspension ; Fibre type composition ; HC IId isoform ; Soleus muscle ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The relationship between the myosin heavy chain (HC) IId isoform and histochemically defined fibre types was investigated in the rat soleus muscle after hindlimb suspension. After 4 weeks of suspension, right and left muscles were removed and fibre type composition and total fibre number were examined by histochemical myosin adenosine triphosphatase staining sections. Myosin HC isoforms were analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis. After the suspension, there was a significant decrease in the percentage of type I fibres and a concomitant increase in that of type IIa fibres. However, the total number of fibres was not affected by suspension. The synthesis of HC IId isoform, which was not found in the control, and the decrease in the ratio of slow type myosin heavy chain isoform (HC I) were observed after suspension. These results would may suggest that the change of fibre type composition was caused by a shift from type I to IIa fibres after suspension. Furthermore, it could be suggested that the synthesis of HC IId isoform occurred during the stage of type shift from type I to IIa fibres.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00599620
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  • 163
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    Dopamine as trace amine in the dorsal root ganglia (1993)
    Springer
    Neurochemical research 18 (1993), S. 965-969 
    Details
    ISSN: 1573-6903
    Keywords: Rat ; dopamine ; immunocytochemistry ; HPLC-ED ; dorsal root ganglia ; sensory neurons ; blood vessels innervation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been shown that in the chick dorsal root ganglion (DRG) about 8% of neurons, belonging to both the A and B classes of sensory neurons exhibit a clear dopamine immunoreactivity. In the present study are reported the results of measurements, by mean of HPLC-electrochemical detection (HPLC-ED), of DA and of the DA metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the rat DRG and their central nerves. Very low levels of DA, about 10 folds lower than the levels found in the dorsal horn of the spinal cord, were found in the DRG. However the levels of DOPAC and HVA were approximately equivalent to the levels found in the cord. The immunocytochemical study performed in parallel has shown that some dopaminergic-immunoreactive fibers in the DRG are located around the blood vessels. Few dopamine-immunoreactive sensory neurons were identified in the DRG and immunoreactive fibers, not linked to blood vessels, were identified in the dorsal root nerves. The present work indicates that there is a dopaminergic innervation of the blood vessels in the rat DRG but that dopamine may also be, as in the chick, a transmitter of primary afferent fibers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00966754
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  • 164
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    Corneal electrode for recording electroretinograms in rats (1993)
    Springer
    Documenta ophthalmologica 83 (1993), S. 175-180 
    Details
    ISSN: 1573-2622
    Keywords: Corneal contact lens electrode ; Electroretinogram ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The corneal contact lens electrode, because of its convenience, has replaced the cotton-wick electrode for recording electroretinograms from patients and animals such as dogs, rabbits, and cats. The cotton-wick electrode, however, remains popular for rat electroretinogram measurements because small contact lens corneal electrodes that fit rat eyes are difficult to fabricate. We prepared corneal electrodes from disposable needles for use in recording electroretinograms from rats. The electrodes were readily prepared, were inexpensive, and were used successfully in six rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01206215
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  • 165
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    Die orthotope Lebertransplantation mit arteriellem Wiederanschluß bei der Ratte — eine detaillierte Beschreibung der Technik und Analyse von Fehlerquellen (1993)
    Springer
    Langenbeck's archives of surgery 378 (1993), S. 73-81 
    Details
    ISSN: 1435-2451
    Keywords: Orthotopic liver transplantation ; Rat ; Suture technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Lebertransplantation (LTX) bei der Ratte ist das am häufigsten untersuchte Transplantationsmodell. In der vorliegenden Studie wird die Technik der orthotopen LTX mit Nahttechnik und arteriellem Wiederanschluß über ein hepatoaortales Segment detailliert beschrieben. Die häufigste Todesursache in der Übungsphase war eine zu lange anhepatische Zeit (〉 20 min), danach beobachtete Komplikationen waren ausschließlich auf eine fehlerhafte Anastomosentechnik zurückzuführen. Der Vorteil der Nahtanastomosen liegt in der physiologischen Gefäßadaption und im Falle von einem arteriellen Wiederanschluß in dem geringeren Operationstrauma im Empfängertier. Trotz der komplizierteren Technik der Nahtanastomose im Vergleich zur Cuff-Technik können anhepatische Zeiten von weniger als 20 min erreicht werden.
    Notes: Abstract Liver transplantation (LTX) in the rat is a frequently used transplantation model. In the present study we give a detailed description of the suture technique for all anastomoses, except the bile duct, with arterialization of the transplanted liver over an aortoceliac segment to the recipient's aorta. Using this technique, we finally achieved survival rates of 80%. During the development stages, the main cause of death was an exceedingly long anhepatic time (〉 20 min); later on, complications occurred only from insufficient anastomoses. The advantage of the suture technique over the cuff technique is that a more physiological anastomosis is obtained with less trauma to the recipient when using rearterialization. Despite the complicated suture technique, the anhepatic time can be well reduced to below 20 min.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00202113
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  • 166
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    Vascular patterns of the saccule of the rat: a microcorrosion cast study (1993)
    Springer
    European archives of oto-rhino-laryngology and head & neck 250 (1993), S. 18-21 
    Details
    ISSN: 1434-4726
    Keywords: Inner ear ; Vestibular system ; Saccule ; Vascularization ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A scanning electron microscope study of corrosion cast preparations of the vessels of the saccule was carried out in adult rats. This method shows the microvasculature of the saccule in the three-dimensional model. As a result of this technique we have been able to demonstrate a particular microvasculature of the saccule in the rat's inner ear. The main blood supply of the saccule consists of the arterioles coming from the vestibulocochlear artery entering the anterior margin of the macula sacculi. A few branches of the anterior vestibular artery enter the macula sacculi from the superior margin. The saccular vein drains the venous blood from a dense capil lary area underneath the striola to the posterior vestibular vein which eventually ends in the vein of the cochlear aquaduct.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00176942
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  • 167
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    Phenol anesthesia of the tympanic membrane in purulent otitis media: a structural analysis in the rat (1993)
    Springer
    European archives of oto-rhino-laryngology and head & neck 249 (1993), S. 470-472 
    Details
    ISSN: 1434-4726
    Keywords: Otitis media ; Tympanic membrane ; Topical phenol anesthesia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the present study, local anesthetics were applied to the tympanic membrane (TM) of rats following experimentally evoked purulent otitis media (POM). The structure of the TM was evaluated 24 h, 2 weeks and 3 months after application of phenol to a discrete are of the right TM. The left ear was used as a control. POM induced swelling of all tissue layers of the pears tensa. The tissues were invaded by inflammatory cells and disintegrated. The fibrous layer also dissolved, leaving spontaneous perforations. However, phenol on inflamed TMs did not further alter the TM structure. These findings infer that the injurious effect of topical anesthesia on the intact TM is more or less negligible when applied to diseased TMs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00168857
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  • 168
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    Synthesis of Glycosylphosphine Oxides and Related Compounds (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 94-112 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The benzyl-protected glycosyl acetates 1, 6, 11, and 15 react with MeOPPh2 under catalysis by TMSOTf to yield diastereoselectively the glycosylphosphine oxides 2, 3, 8, 12, 13, and 16, with a strong preference for the 1,2-cis-configurated anomers. Hydrogenolysis of the major products gave the crystalline, unprotected phosphine oxides 4, 9, 14, and 17, of which 4 was transformed in to the acetate 5, and 9 into the benzoate 10. The benzylated phosphine oxides 4, 8, 12, and 16 were reduced with Cl3SiH in the presence of a tertiary amine to form the phosphines 18, 21, 24, and 26, which were transformed into the phosphine sulfides 19, 22, 25, and 27. Moreover, 18 and 21, were characterized as the borane adducts 20, and 23. The structure of the (arabinofuranosyl)phosphine oxide 12, the corresponding sulfide 25, and of the borane complex 20 were established by X-ray analysis. According to NMR spectroscopy, the equatorial pyranosylphosphine oxide 8, the sulfide 22, and the borane complex 23 adopt a 4C1 conformation. The axial phosphine oxide 2 is a flattened 4C1, the sulfide 19 exists as a B2,5, and the borane complex 20 is a flattened 4C1 in the solid sate and a B2,5 in solution. Thus, the conformational behavior of these α-D-glucopyranose derivatives reflects the steric requirement of the P-substituents.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760104
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    Nucleotides. Part XXXIXPart XXXVIII: [1]. Synthesis of arabinonucleoside phosphoramidite building blocks (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 158-167 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: High-yield chemical syntheses of phosphoramidite building blocks of the four arabinonucleosides aUrd (1), aCyd (2), aAdo (3), and aGuo (4), suitable for (3′-5′)oligoarabinonucleotide synthesis are described. The problem of 2′-hydroxy group protection was solved by introduction of the versatile 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) residue, which was also used for aglycon protection.
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760110
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    Reactions of Carbonyl Group with Nitroso Compounds: Reaction of Formaldehyde with Substituted Nitrosobenzenes (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 131-138 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Formaldehyde reacts with substituted nitrosobenzenes giving the corresponding N-phenylhydroxamic acids. A mechanism involving three sequential steps in this reaction is proposed. The first step is the nucleophilic attack of the nitroso group on the carbonyl group which leads to the formation of the unstable tetrahedral zwitterionic intermediate. This step is followed by the proton transfer to the zwitterionic intermediate to form more stable nitrosocarbinolic cation intermediate, which in the subsequent step undergoes the rate-controlling elimination of proton from the C-atom of nitrosocarbinolic group, leading to the final product, hydroxamic acid. The first and the second step appear to be reversible. The experimental evidence obtained, which is the basis for such a description of the investigated reaction, includes: (a) the order of reactivity of substituted nitrosobenzenes, as demonstrated by the plot of log kobs vs. σ Hammett parameters with slope of -1.74; (b) the observation of a general-acid catalysis; (c) the observation of the inverse solvent deuterium isotope effect of ca. 1.8 in the reaction; (d) the observation of kinetic primary deuterium isotope effect of ca. 8 related to the ‘water’ reaction in the reactions of formaldehyde with substituted nitrosobenzenes; (e) the observation of general-base catalysis in the reaction; (f) the observation of the kinetic primary deuterium isotope effect of ca. 2.1 for the acetate-ion-catalyzed reaction.
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760107
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    Total Synthesis of the Gastroprotective Substance AI-77-B and of Analogues‘Naked Sugar’ as Synthetic Intermediates, Part XXIII. Part XXII, see [1]. This work was presented at the autumn meeting of the Swiss Chemical Society, Bern, Oct. 18, 1991. (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 222-240 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The Diels-Alder adducts 8 of furan to 1-cyanovinyl acetate were converted into (Methyl 3-chloro)-5-O-(3-chlorobenzoyl)-2, 3-dideoxy-α-dl-arabino-hexofuranosid)uronic acid ((α)-18a) and into (methyl 3-azido-5-O-(3-chlorobenzoyl_-2,3-dideoxy-α-dl-ribo-hexofuranosid)uronic acid ((α)-41a). These compounds were condensed to (3S)-3-[(1′S)-1′-amino-3′-methylbutyl]-3,4-dihydro-8-hydroxyisocoumarin hydrochloride ((-)-2); the resulting mixtures of diastereoisomeric amides were transformed and separated to give the gastroprotective substance AI-77-B((-)-1) and analogues.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760116
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    A New Synthesis of Benzylidene AcetalsReported in part at the ‘XVIth International Carbohydrate Symposium’, Paris, July 5-10, 1992. (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 211-221 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Aryl-halo-diazirines react under basic conditions with 1,3-cis-, 1,2-cisand 1,2-trans-diols to give acetals. Yields are high. Diastereoselectivities depend upon the diol and upon the reaction conditions. Thus, reaction of the 1,3-cis-diol 1 (Scheme 1) with 2 gave 3 as a single diastereoisomer. The 1,2-cis-diols 4 and 7 led to the endo- and exo-acetals 5/6 (93:7) and 8/9 (ca.10:1), respectively, The 1,2-trans-diols 10, 16, and 19 reacted with 2 to afford 11/12 (90:10), 17/18 (1:1), and 20/21 (6:1), respectively. Reaction of the (4-nitrophenyl)diazirine 13 with 10 at higher temperatures yielded 14/15 (6:4). The uracil moiety, the acetamido group, and the enol-ether moiety are compatible with the reaction conditions. The diastereoselectivity is rationalized on the basis of a reaction sequence involving alkoxy-halogen exchange, which is regioselective or not, thermolysis of the ensuing alkoxydiazirine(s), protonation of the alkoxycarbene to form an (E)-configurated oxycarbenium ion, and attack of the neighboring oxy or hydroxy group, which is only possible for a limited range of conformers.
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760115
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    Synthese chiraler Kobalt-Komplexe mit planoid-tetradentatem Ligand-SystemEin Teil der hier publizierten Ergebnisse wurden von R. H. am ‘Sixth IUPAC Symoposium on Organometallic Chemistry Directed Towards Organic Synthesis’ in Utrecht/Holland (29. 8. 1991) vorgetragen. (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 353-371 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Synthesis of Chiral Cobalt Complexes with Planoid-Tetradentate Ligand SystemThe synthesis of a series of Cbl-related, achiral CoIII complexes 9a-c as well as enantiomerically pure, C2-symmetric CoIII complexes 15 and 18, is reported (Schemes 3, 5, and 7). The crystal structures of 9c and 15 were determined. Complex 18 acts as an enantioselective catalyst in the isomerization of 1,4-epiperoxides to hydroxycycloalkenones.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760120
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  • 174
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    Enantioselektive Synthese von Allyl- und Propargylaminen durch nucleophile 1,2-Addition an chirale Aldimine. Preliminary communication (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 402-406 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Enantioselective Synthesis of Allyl- and Propargylamines via Nucleophilic 1,2- Addition to Chiral AldininesThe asymmetric Synthesis of allylamines and propargylamines 5 in high enantiomeric purity (e.e. ≤ 97%) is described. Key step is the 1,2-addition of organocerium reagents to chiral α,β-unsaturated aldimines 3 to produce secondary animes 4. The Chiral auxiliary (S,S)-2 is removed in three steps, affording the title compounds 5, useful bifunctional building blocks and compounds of pharmaceutical interest.
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760123
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    The Synthesis of Natural Acetylenic Compounds from Eutypa lata (Pers; F.) TUL (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 425-430 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The synthesis of a series of novel acetylenic compounds 1-7, isolated recently from the fungus Eutypa lata, is described. The crucial step is the coupling reaction between a protected aryl halogenide and the acetylenic chain as a cuprous acetylide (Scheme 1). A more efficient method using bis(triphenylphosphine)palladium dichloride ([Pd(PPh3)2Cl2]) as catalyst was also carried out with success.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760126
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    C2-Symmetrical Pyrrolidine Derivatives Chiral Auxiliaries in Radical Chemistry (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 441-450 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Fumaramides 3b and 3c bearing the C2-symmetrical pyrrolidine moieties (2R,5R)-2,5-bis(methoxymethyl)pyrrolidine (2b) or 1,3:4,6-di-O-benzylidene-2,5-dideoxy-2,5-imino-L-idit (2c), respectively, as a chiral auxiliary lead to high diastereoselectivities in radical reactions (‘tin method’;Scheme 1). Removal of the chiral auxiliaries affords the corresponding alkylated fumaric acids Scheme 2. Single-crystal X-ray structures of 3b and 3c support arguments that lead to the model of 1,4-stereoinduction.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760128
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    Synthesis and Biological Evaluation of 14-Alkoxymorphinans. Part 9Part 8:[1].. 14-O-ethyl-5-methylnaltrexone, and opioid antagonist with unusual selectivity (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 476-480 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: 14O-Ethyl-5m-ethylnaloxone (7) and 14O-ethyl-5-methylnaltrexone (8) have been prepared starting from 14O-ethyl-5-methyloxycodone (9) in several steps. Both, 7 and 8, were found to be opioid antagonists in vitro and in vivo. Compound 7 exhibited some selectivity for μ opioid receptors, whereas compound 8 did not show selectivity for any of the receptor types. In the AcOH-writhing antagonism test, 8 was not able to antagonize morphine-induced antinociception, but antagonized fentanyl- and sufentanil-induced antinociception.
    Additional Material: 4 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760131
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    On the Novel Free Porphyrins Corallistin B, C, D, and E: Isolation from the demosponge Corallistes sp. of the Coral Sea and Reactivity of Their Nickel 55 (II) Complexes toward Formylating Reagents (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 1489-1496 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Reported here are the novel free porphyrins corallistin B, C, D, and E, isolated as methyl esters 2a, 3a, 4a, and 5a, respectively, from the sponge Corallistes sp. (Lithistida) collected at the basis of the south New Caledonian coral reef. A protocol is also established for formylation of their NiII complexes, which show a different reactivity pattern toward DMF/POCl3 from metal complexes of deuteroporphyrins. Together with corallistin A, Previously isolated as the methyl ester 1a, and the known deuteroporphyrin IX (isolated as 6a) also present in the sponge, the new corallistins, which may be thought to derive from protoporphyrin via heme, account for an amazing 60% of the EtOh extract from the sponge.
    Additional Material: 3 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760410
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    Synthese von selektiv N- funktionalisierten Polyamin-Derivaten (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 1511-1519 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Synthesis of Selectively N-Functionalized Polyamine DerivativesA threefold differently protected derivative 8 of the triamine spermidine (2) has been prepared in three steps starting from propane-1,3-diamine (1). The protected spermidine derivative 8 was converted to its spermine analogue 12, a useful polyamine intermediate. In a convergent way, the fourfold differently protected derivative 18 of the tetraamine spermine (3) has been obtained by coupling the two different and separately prepared propane-1,3-diamine units 15 and 17. Spermidine derivative 19 and spermine derivative 20, both selectively protected at both primary amino groups, have been Prepared from the free polyamines 2 and 3, respectively, in a direct approach.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760412
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    Oxidative Coupling Of 2-Alkyl-6,6-dimethylpentafulvenyl AnionsCoupling Reactions, Part 11; Part 10: [1] (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 1497-1510 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Cucl2-Induced oxidative coupling of 2-(tert-butyl)-6,6-dimethylpentafulvenyl anion 9 predominantly takes place at C(7) and C(5) to give [7-7] and [7-5] coupling products 15 and 16 in 35 and 47% yields, respectively (Scheme 3) whose structures are elucidated from 1D- and 2D-NMR analysis. Compared with the product distribution observed for 6,6-dimethylpentafulvenyl anion 2 (Scheme 1), no coupling at C(2)/C(3) of 9 is observed. This means that, besides electronic effects, steric effect are also important in oxidative couplings of fulvenyl anions. The same couplings occur in the case of 2,3-bis(6,6-dimethylfulven-2-yl)-2,3-dimethylbutane dianion 10 as well but, due to electronic as well as conformational effects (Scheme 5), intermolecular coupling (to give polymers 17, Scheme 4) is strongly favored over intermolecular coupling. Mechanisms explaining base-catalyzed isomerization 15a ⇄ 15b ⇄ 15c (Scheme 6) as well as isomerization 16a ⇄16b (Scheme 7) are proposed.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760411
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    Structural Chemistry of Chiral Complexes. NMR and X-ray studies on Rh1 compounds of (S)-1-[bis(p-methylphenyl)phosphino]-2-[(p-methoxybenzyl)amino]-3-methylbutane (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 1520-1538 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The Rh1(diolefin)complexes [Rh(nbd)(2)][PF6] [Rh(1,5-cod)(2)][PF6], and [Rh((Z)-α -acetamidocinnamic acid)(2)][PF6] (2 = the chiral P,N-ligand (S)-1-[bis(p-methylphenyl)phospino]-2-[p-methoxybenzyl)amino]-3-methylbutane have been prepared and characterized. These complexes exit as a mixture of isomers arising from different five-membered-ring conformations and diastereoisomers due to both the prochiral nitrogen and olefin ligands. The three-dimensional solutions structures of these complexes have been studied with the specific aim of understanding how the chiral pocket is built. Aspects of the exchange dynamics and their possible relevance to homogeneous hydrogenation are discussed The solid-state structure for the nbd complex, [Rh(nbd)(2)][PF6], as well as detailed one- and two-dimensional 31P-, 13C-, and 1H-NMR results are presented.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760413
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  • 182
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    Template-Assembled Synthetic Proteins (TASP). Cyclic Templates with Incorporated Turn-Inducing Mimics (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 1539-1563 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The 8-amino-5,6,7,8-tetrahydronaphth-2-oic acid (1), 8-(aminomethyl)-5,6,7,8-tetrahydronaphth-2-oic acid (2), and 8-(aminomethyl)naphth-2-oic acid (3) were synthesized in their protected forms as turn-inducing dipeptide mimics. Two of them (2 and 3) were incorporated into a novel type of cyclic, peptide-based structures (see 21 and 34-36) designed as templates for the synthesis of TASP molecules.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760414
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  • 183
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    Enantioselective Synthesis of 3- Azabicyclo[4.3.0]nonane Alkaloids (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 1591-1607 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The stereospecific synthesis of the monoterpene alkaloids (-)-α-skytanthine ((-)-2), (-)-N -demethyle-δ-sky-tanthine((-)-7), and (+)-epidihydrotecomanine (+)-4 was achieved from a common intermediate 22, which in turn was obtained from (1R,4S,1′S)-2-(1′-phenylethyl)-2-azabicyclo[2.2.1]hept-5-ene (10),via a ketene aza-Claisen rearrangement. The piperidine derivative (+)-31, formally the aza-analogue of (+)-isoiridomyrmecin, was also obtained from the same intermediate 22.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760416
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  • 184
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    Degradation of Cephaloridine on Alkaline Hydrolysis (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 1619-1625 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A kinetic study on the alkaline hydrolysis of cephaloridine (1) at pH 10.5 and 37° was carried out using ion-pair reversed-phase HPLC. The main resulting degradation products, the 7-epimer 2 of 1, the Δ2-isomer 3 of 1, and the 3-methylidene compound 4 were identified. The presence of a pyridinio group at C(31) results in a slightly increased formation constant for the 3-methylidene compound 4 and the 7-epimer 2, and introduces a new reaction: the isomerization of the double bond at C(3) in the dihydrothiazine ring to C(2).
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760418
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  • 185
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    Internal Nucleophilic Termination in Acid-Mediated Polyene Cyclisations: Synthetic access to methyle homologs of (±)-Ambrox® and its diastereoisomers (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 1608-1618 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Treatment of ten monocyclic dienols 8-11 with an excess of fluorosulfonic acid in 2-nitropropane at -90° afforded diastereoisomeric mixtures of racemic tricyclic ethers 12-14 in 81-91% yield (see tables 1 and 2). These transformations represent further examples of biomimetic acid-mediated cyclisations in which an OH group serves as the internal nucleophilic terminator. A non-synchronous process is postulated, and the examples described strongly re-inforce our working mechanistic hypothesis, whereby the stereochemical course of cyclisation is directed by the orientation of the side chain vicinal to the intermediate cyclohexyl cation (see Schemes 4 and 5). It is also demonstrated that the efficiency of this process is independent of the nature of the OH group, which may be primary, secondary, or tertiary. In addition, the organoleptic properties of 12-14, Me homologs of known odorants such as Ambrox® ((-)-3a) and its diastereoisomer, are briefly discussed.
    Additional Material: 4 Tab.
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    URL: http://dx.doi.org/10.1002/hlca.19930760417
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  • 186
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    Modification of Cyclosporin A (CS)Cyclosporine (CS) is defined as the cyclosporin-A structure to facilitate nomenclature of other cyclosporine derivatives. Thus, cyclosporin C becomes [2-(L-threonine)]cylosporine and is abbreviated [Thr2]CS. This convention avoids the use of the alphabet for specification of cyclosporine derivatives (see below, references to previous work on CS).: Generation of an enolate at the sarcosine residue and reactions with electrophiles (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 1564-1590 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Strong bases (lithium diisopropylamide (LDA) or BuLi) convert cyclosporin A (CS) to hexalithio derivative containing a Li alkoxide, four Li azaenolate, and one Li enolate units. The Li6 compound is solubilized in tetrahydrofuran (THF) by addition of excess LDA or LiCl. Reactions with electrophiles (alkyl halides, aldehydes, ClCO2R, CO2, (RS)2, D2O) at low temperatures give products containing new side chains in amino-acid residue 3 of the cyclic undecapeptide (see 1-13, Schemes 1, and 2, and Figs. 1 and 2) in moderate to high yields and, with Re- or Si-selectivities, depending upon the conditions of lithiation of up to 7:1, Pure CS derivatives (Scheme 2, Table 1 in the Exper. Part) can be isolated by column chromatography. N-Alkylations or cleavage of the peptide backbone by carbonyl addition occur only at higher temperatures and/or with prolonged reaction times (see 14 and 15 in Scheme 4). Very little or no epimerization of stereogenic centers occurs under the conditions employed. Possible reasons for the feasibility of these surprizing conversions of CS are discussed (Schemes 4 and 5 and Fig. 3). For comparision, [MeAla3]CS (2b) and [D-MeAla3]CS (2a) were also prepared by conventional peptide synthesis in solution (Schemes 6 and 7). Their 1H- and 13C-NMR spectra are compared with those of CS (Table 2 in the Exper. Part).
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760415
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  • 187
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    Über Diels-Alder-Reaktionen des C60-Fullerens Vorläufige Mitteilung (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 1626-1631 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: On Diels-Alder Reactions of the C60-FullereneWe report on the regioselective [4+2] cycloaddition of Buckminsterfullerene C60(1) at room temperature with 2,3-dimethylbuta-1,3-diene and with the monoterpene 7-methyl-3-methylideneocta-1,6-diene (= myrcene) and on the spectroscopic characterization of the corresponding crystalling monoadducts 2 and 3. According to these experiments, 1 acts as a reactive dienophile, which can be functionalized regioselectively under mild and controlled conditons.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760419
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  • 188
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    Die massenspektrometrische Wasserabspaltung aus makrocyclischen Amino-ketonenHerrn Prof.Max Viscontini zum 80. Geburtstag gewidmet (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 1636-1648 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The Mass Spectral Loss of Water from Macrocyclic Amino-ketonesMacrocyclic oxo-lactams containing an N-alkylamino side chain are stable natural products. Their electron-impact mass spectra are characterized by intensive [M - H2O]+ signals, the molecular ion signal itself is missing. Under electrospray ionization conditions, on the other hand, the [M + 1]+ ion is the only detected signal. The loss of water is explained in terms of an internal (thermal) Schiff-base formation, leading to a e.g. bicyclo[11.9.4]-system. The alcohol corresponding to the macrocyclic ketones and/or lactams show an expected mass-spectral behavior following well known rules.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760421
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  • 189
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    Definitive Proof for the Operation of Isotopically Sensitive Branching (‘Metabolic Switching’) in FeI-Mediated C—H Bond Activation in the Gas Phase Short CommunicationDedicated to Professor M. H. Zenk, Universität München, on the occassion of his 60th birthday (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 1632-1635 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Rigorous regio- and stereospecific labeling experiments are performed to demonstrate the operation of the previously suggested operation of ‘isotopically sensitive branching’ in FeI-mediated C—H bond activation. For the hexane-1,6-diol/Fe+-complex, it is shown that dehydrogenation involves specifically the central C(3)/C(4) position, and the study of the stereospecifically labeled D,L- and meso-[3,4-D2]-isotompomers 1e and 1f demonstrates that dehydrogenation proceedes via two competing pathways (i.e. ‘anti’- vs. ‘syn’-route). The contribution of these routes to the product formation is - due to a kinetic isotope effect - controlled by the relative configuration at the labeled positions C(3)/C(4). For the D,L-form 1e, we estimate a ratio of 49:1 in favor of the ‘anti’-route; due to an isotope effect, this ratio drops to 4.3:1 for the meso-form 1f.
    Additional Material: 2 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760420
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  • 190
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    Zur Herstellung von PQQ in kg-Mengen (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 1667-1673 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Preparation of PQQ in the kag ScaleThe improvement of the PQQ synthesis according to the method of Corey and Tramontano allows the preparation of the triester of this cofactor in the kg scale with an overall yield of 13% (average 78% per step), without a bottleneck in the sequence and with crystalline, analytically pure intermediates. The new purification of free PQQ from conc. H2SO4 is remarkable with respect to the application as well as to the stability of this natural product.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760423
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  • 191
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    Synthesis and Solvent Effects on the Conformation of Hymenistatin 1 (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 1649-1666 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The cyclic octapeptide cyclo(-Pro-Pro-Tyr-Val-ProLeu-Ile-Ile-) (1), isolated from the Hymeniacidon sponge, was synthesized and examined conformationally using NMR and molecular-dynamics simulations. Most structural parameters of synthetic 1 are in accord with those reported for the isolated material. Our study indicates some small but significant differences in the assignment of the 1H- and 13C-NMR resonances from those of the natural material. The Conformation was determind in both CHCl3 and DMSO using 1H-NMR and molecular-dynamics simulations. Both NOE's and coupling constants were used as experimental restraints during the simulations which utilized explicitly the same solvent as in the NMR study. The differences in the interaction of the solvent with 1 were examined, providing insight into the observed differenced in conformation. The dominant conformation contains a ßVIa turn about Ile8-Tyr3 including a Pro1-Pro2 cis-peptide bond and a ßI or ßII turn about Val4-Ile7 in CHCl3 and DMSO, respectively.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760422
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  • 192
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    Das Diazo-chinon von PQQ als mögliches Reagenz für die Kartierung von Chinoproteinen mittels PhotoaffinitätsmarkierungDer Inhalt der vorliegenden Publikation war Teil einer Präsentation am ‘2nd Interational Symposium on PQQ and Quinoproteins’, Nov.19-22, 1991, Yamaguchi, Japan. (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 1674-1677 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The Diazo-quinone of PQQ as a Possible Reagent for Mapping Quinoproteins by Photo-affinity LabelingPQQ is an organic redox cofactor found in a class of enzymes called quinoproteins. The synthesis and the photochemistry of the diazo-quinones of PQQ and PQQ-triester are described. The photogenerated Wolff-rear-rangement products have been caught with water and methanol as model nucleophiles. The products show a strong fluorescence. The diazoquinone of PQQ may be considered as possible reagent for mapping quinoproteins by photo-affinity labeling.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760424
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  • 193
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    Radical Rearrangements of 2-O-(Diphenoxyphosphoryl)glycosyl Bromides (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 1687-1701 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A variety of 2-deoxy-1-O-diphenoxylphosphoryl-hexopyranoses were generated in situ by a radical 2→1 migration of the phosphate group. The structures of the reactive rearrangement products were fully elucidated by NMR spectroscopy. Rate constants for this new rearrangement were determined fro a variety of substrates.
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760426
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  • 194
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    Derivatisierung von PQQ und PQQ-Triester für den Nachweis von PQQDer Inhalt der vorliegenden Publikation war Teil einer Präsentation am ‘2nd International Symposium on PQQ and Quinoproteins’, Nov. 19-22, 1991, Yamaguchi, Japan. (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 1678-1686 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Formation of derivatives of PQQ and PQQ-Triester for the Detection of PQQPQQ is an organic redox/cofactor found in a class of enzymes called quinoproteins. It has been reported that materials like milk, egg yolk, vinegar, beer, serum, urine, and biological tissues contain little amounts of PQQ. To facilitate studies on PQQ, a simple detection of PQQ could be extremely useful. For this purpose, we describe in this paper some adducts of PQQ or PQQ-triester with 1,2-diamines, 2,4-dihydroxyaniline, pyrrole, indole as well as an oxidation product of PQQ. UV and fluorimetric detections of these colored products show that this method is relatively sensitive. The reaction of PQQ-triester with (MeO)3P to the phosphole adduct 13 is of great importance: the use of [32P]-labeled trialkyl phosphites will make this reaction an extremely sensitive method to detect PQQ.
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760425
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  • 195
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    Dehydroalanine-Containing Peptides by AcOH-Elimination from O-Acetylserine Residuces with DBU/LiClO4 in Tetrahydrofuran (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 1702-1714 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The elimination of H2O from serine residues in peptides was found to be feasible by the following two steps: O-acylation with AcCl/pyrideine in CH2Cl2 and treatment with an imidine base (DBU or DBN) in THF in the presence of large amounts of LiClO4 (10 examples). Other Li salts such as LiBr and LiCl can also be used. No epimerization of the amino acid residues in te peptide could be detected under these conditions. Thus, a simple method for the preparation of peptides with dehydroalanine residues in high yield, directly from serine-containing precursors, is available.
    Additional Material: 2 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760427
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  • 196
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    The Homoconjugated Electron-Releasing Carbonyl Group of 1-Methylbicyclo[2.2.1]hept-5-en-2-one. Regioselective syntheses of 5-chloro- and 6-chloro-1-methylbicyclo[2.2.1]hept-5-en-2-one (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 2338-2343 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Syntheses of (±)-2-exo-cyano-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl acetate (1) and of (±)-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one (2) are reported. The additon of PhSeCl to 1 afforded (±)-5-endo-chloro-2-exo-cyano-1-methyl-6-exo-(phenylselenenyl)-7-oxabicyclo[2.2.1]hept-2-endo-yl acetate (6), whereas 2 added to PhSeCl with the opposite regioselectivity giving (±)-6-endo-chloro-1-methyl-5-exo-(phenylselenenyl)-7-oxabicyclo[2.2.1]heptan-2-one (7). These adducts were converted into 5-chloro-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one (9) and 6-chloro-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one (10), respectively.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760619
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  • 197
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    Bei der Redaktion eingetroffene Bücher (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 1027-1027 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760226
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  • 198
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    Synthese eines 1,2-trans-konfigurierten, äquatorialen Glycosyl-phosphonat-Analogen von D-myo-Inositol-1,4,5-trisphosphat (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 1013-1025 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Synthesis of a 1,2-trans-Configurated, Equatorial Glycosylphosphonate Analogue of D-myo-Inositol 1,4,5-TrisphosphateThe diphosphonate analogue 3 of D-myo-inositol 1,4,5-trisphosphate (1), a 1,2-trans-configurated, equatorial glycosylphosphonate, was synthesized and characterized as its hexasodium salt 3a. In a first approach, the silylated galactal 4 (Scheme 1) was transformed into the oxirane 5 and hence, by treatment with Me3SiP(OMe)2, into a mixture of the glycosylphosphonate 6 and its silyl ether 7. This mixture was desilylated and then treated with acetone and FeCl3 to yield 8 and 9 (64 and 22%, resp., from 4). In a second approach, the acetates 11/12(Scheme 2) were treated with P(OMe)3/Me3SiOTf in MeCN to afford the anomeric glycosylphosphonates 16/17 (1:1, 60%), while the trichloroacetimidate 10 gave mostly the αD-anomer 16. The αD-anomer 20 was obtained from 12 and P(OPh)3. The highest yield of a β-Dphosphonate was realized by treating 12 with the cyclic phosphite 15 (→ 18/19, 40% each). The β-D-phosphonate 17 was debenzylated (→21) and protected to give 8. Transformation of 8 into the bromide 22 (43%) proved difficult due to the facile demethylation of thephosphonate, and was best followed by treatment of the crude product with CH2N2 and 2,2-dimethoxyporpane. Phosphorylation of 22 yielded 41% of the (dimethoxyphosphoryl)phosphate 23. The conditions of the Arbuzov reaction slowly converted the bromide 23 into the bis(phosphoryl)phosphate 24 (69%), which was then deprotected. The resulting 3 was purified via the ammonium salt and transformed into 3a (72%).
    Additional Material: 2 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760224
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  • 199
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    Synthetische Analoga von niedermolekularen Spinnentoxinen mit Acyl-polyamin-Struktur (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 1167-1181 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Synthetic Analogues of Low-Molecular-Weight Acyl-polyamine Spider ToxinsLow-molecular-weight spider and wasp toxins are selective inhibitors of glutamate receptors of the central nervous system and consist of a polyamine backbone and one or several carboxylic acids and/or amino acids linked by a peptide-like bond. The syntheses of twelve analogues of spider and wasp toxins are described (10a-c, 15a-c, 20a-c, 25a-c) having the general structure of acyl, arylacyl, or heteroarylacyl → DL-alanyl → ω-aminoacyl → N1-spermidine, with variation in the acyl and the ω-aminoacyl part.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19930760304
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  • 200
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    The Chemistry of Coumarin Derivatives. Part 5.Part 4: [1]. Unusual course of the reaction of 4-hydroxycoumarin and aliphatic aldehydes (1993)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 1194-1202 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The reaction of 4-hydroxycoumarin and certain aliphatic aldehydes affords 1:1 or complex 2:2 adducts besides (or in place) of the expected 2:1 bis(coumarin) adducts. Reaction with heptanal, cyclohexanecarbaldehyde, and pivalaldehyde are reported as representative. The structure of the reaction products was established by spectroscopical techniques, including X-ray analysis, and their formation was mechanistically rationalized. Some of the 1:1 adducts are synthetically useful for the preparation of 3-alkyl-4-hydroxycoumarins.
    Additional Material: 2 Tab.
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    URL: http://dx.doi.org/10.1002/hlca.19930760306
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