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  • Articles: DFG German National Licenses  (41)
  • Life and Medical Sciences  (28)
  • Dopamine  (5)
  • Chemical Engineering  (4)
  • General Chemistry  (4)
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  • Articles: DFG German National Licenses  (41)
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  • 1
    ISSN: 1432-2072
    Keywords: Latent inhibition ; Dopamine ; Ondansetron ; 5HT3 antagonists ; Amphetamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Latent inhibition (LI) is a behavioural phenomenon whereby preexposure to a stimulus without reinforcement interferes with the formation of subsequent associations to that stimulus. Using preexposure to a tone stimulus which subsequently serves as a conditioned stimulus for suppression of licking, we have confirmed that LI is disrupted by a low dose of amphetamine. Haloperidol was able to prevent this effect of amphetamine. Ondansetron, a selective and potent 5HT3 receptor antagonist, was also shown to be effective at blocking the amphetamine-induced disruption of LI at a dose of 0.01 mg/kg, but not at 0.1 mg/kg. In addition, it was demonstrated that ondansetron could enhance LI; using only ten preexposures, no LI was obtained in the saline group, but was apparent in animals given ondansetron, an effect which has been previously shown with haloperidol. Haloperidol, at the higher dose used, reduced suppression of licking, however, ondansetron at the effective dose had no such effect. It is concluded that ondansetron is able to attenuate increases in dopamine activity, produced pharmacologically with amphetamine without affecting baseline dopamine activity. The implications of these findings for a possible antipsychotic action of ondansetron are discussed.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Nicotine ; Latent inhibition ; Dopamine ; N. accumbens ; Haloperidol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Latent inhibition (LI) is a cognitive process whereby repeated exposure of a stimulus without consequence impedes the formation of subsequent associations with that stimulus. A number of studies in the rat have reported that LI is impaired by moderate systemic doses of amphetamine, an effect believed to be mediated via dopamine (DA) release in the nucleus accumbens. We and others have reported that nicotine has a selective effect in releasing DA in the accumbens rather than the caudate nucleus. We have therefore examined the ability of nicotine to disrupt LI, using a conditioned emotional response paradigm. Pre-exposure of a tone stimulus impaired subsequent conditioning between that stimulus and mild footshock, as indexed by suppression of licking by the tone subsequently presented alone. This LI effect was prevented, by an effect confined to the pre-exposed group, by doses of 0.4 or 0.6 mg/kg nicotine SC, which are accumbens selective, given before pre-exposure and before conditioning. The effect of nicotine in disrupting LI was prevented by prior administration of haloperidol at a dose (0.5 mg/kg) reported to reverse the disruptive effect of amphetamine on LI. Although the amphetamine effect requires two administrations, the effect of two administrations of nicotine was reproduced by a single dose of nicotine given before conditioning, but not by a single dose before pre-exposure. The results are discussed in relation to studies in human control and schizophrenic subjects, which suggest that increased DA activity in humans is also associated with impaired LI. The results indicate that nicotine does indeed increase functional DA activity in the rat accumbens; the consequent disruption of LI critically depends upon an action at the time of conditioning, and is independent of processes which occur during pre-exposure. In more general terms, this indicates the potential of drug experiments to complement behavioural studies on the mechanism of latent inhibition.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 63 (1979), S. 273-280 
    ISSN: 1432-2072
    Keywords: Dopamine ; Lateral inhibition ; Attention ; Schizophrenia ; Model for schizophrenia ; Schizophrenic symptoms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A hypothesis is briefly discussed proposing that schizophrenic symptoms are due to a breakdown in a mechanism by which conscious attention is limited and directed. It is shown that this mechanism can be modelled in terms of a simple nerve network in which every channel inhibits all the others. Failure of this inhibition would cause the defect hypothesised to occur in schizophrenia. It is shown that if dopamine is given a central role as transmitter in such a network then the various predictions about the biochemistry of schizophrenia that follow are not only consistent with the evidence for the ‘dopamine theory’ of schizophrenia, but also with much of the evidence held to be contrary to that theory. While not purporting to be an experimentally validated description of schizophrenia, this model goes beyond the single amine theories of schizophrenia and links dysfunctions in amine systems with specific behavioural control mechanisms. Given the current state of knowledge, such models can make only limited predictions about the biochemistry of schizophrenia. However, an attempt to link behavioural and biochemical systems in this way will be crucial for the development of viable animal models of schizophrenia.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2072
    Keywords: Key words Methamphetamine ; Dopamine ; Serotonin ; Phentermine ; Fenfluramine ; Drug-discrimination ; Self-administration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To analyze the involvement of dopamine (DA) and serotonin (5-HT) release in the stimulus properties of methamphetamine, two amphetamine analogs that selectively release either brain DA (phentermine) or 5-HT (fenfluramine) were tested for their ability to substitute for methamphetamine in rats discriminating methamphetamine (1.0 mg/kg) from saline. They were subsequently tested for their ability to alter IV methamphetamine (0.06 mg/kg per injection) self-administration in the same species when given as a pretreatment. The DA releaser phentermine, like methamphetamine itself, decreased methamphetamine self-administration (to 70% of baseline responding), but only at a dose of 3.0 mg/kg that fully generalized to the methamphetamine stimulus in the discrimination study. The 5-HT releaser fenfluramine attenuated methamphetamine self-administration to a much larger extent than phentermine (to 37% of baseline responding) at a dose of 1.8 mg/kg that did not generalize to methamphetamine and did not decrease rate of responding in the discrimination study. Tolerance developed to the inhibitory effect of 1.8 mg/kg fenfluramine on methamphetamine self-administration when it was given repeatedly over four consecutive daily sessions. The fenfluramine-induced decrease in methamphetamine self-administration was also attenuated when it was given together with the small 1.0 mg/kg dose of phentermine. These results suggest that DA release plays a dominant role in the discriminative stimulus effects of methamphetamine. However, stimulation of 5-HT release can strongly modify methamphetamine self-administration.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2072
    Keywords: Key words Drug discrimination ; Microdialysis ; Dopamine ; Serotonin ; Phentermine ; Fenfluramine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Clinical case studies suggest that combined administration of the serotonergic agent fenfluramine (FEN) and the weak amphetamine-like anorexic agent phentermine (PHEN) may be useful in the treatment of alcohol and cocaine addictions. The present experiment examined the nature of the interaction between the two agonists using the drug discrimination paradigm. In vivo microdialysis served to examine the neurochemical profile of dopamine and serotonin release in the nucleus accumbens. In conscious rats, acute injections of FEN (1.0–2.0 mg/kg IP) or PHEN (1.0–2.0 mg/kg IP) selectively elevated levels of serotonin and dopamine in the nucleus accumbens, respectively. A mixture (1 mg/kg of each) increased levels of both amines by similar magnitudes to those observed with each individually. Three groups of Sprague-Dawley rats were trained to discriminate (1) FEN (1.0 mg/kg IP) alone, (2) PHEN (1.0 mg/kg IP) alone or a mixture (3) PHEN+FEN (1 mg/kg of each, IP) from saline under a fixed ratio (FR-10) schedule of food reinforcement. Rats acquired the mixture discrimination rapidly, while for the other groups the training dose had to be increased to 2.0 mg/kg to attain stimulus control. The individual components of the mixture at the training dose generalized partially to the mixture, and complete generalisation was observed following 3.0 mg/kg FEN or PHEN. Rats trained to discriminate the individual components showed respective cross-generalisation profiles. Generalisation to cocaine (0.3–10.0 mg/kg IP), amphetamine (0.1–3.0 mg/kg IP) and nicotine (0.1–0.8 mg/kg SC) was greatest in the MIX-trained rats, while partial or no generalisation was observed in rats trained to discriminate the individual compounds. From the present results, it may be concluded that the two drugs given as a mixture do not produce a novel cue. Rather, these aminergics appear to interact additively. Furthermore, the dual stimulation of the amines by the mixture may be the basis for the cueing effects of the FEN+PHEN drug mixture, and its effectiveness in treating drug addictions.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Cell Motility and the Cytoskeleton 5 (1985), S. 175-193 
    ISSN: 0886-1544
    Keywords: primary cilia ; connective tissues ; secretory organelles ; extracellular matrix ; cybernetic probe ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: More than 300 primary cilia have been identified electronmicroscopically in a variety of embryonic and mature connective tissue cells. To further define the enigmatic function of these cilia, we examined the interrelationships between the basal apparatus and cytoplasmic organelles and the ciliary shaft and the extracellular matrix. The basal diplosome was consistently associated with the secretory organelles including the maturing face of the Golgi complex, Golgi vacuoles and vesicles, the microtubular network, the plasma membrane, and coated pits and vesicles. Small vesicles and amorphous granules were also observed within the ciliary lumen and adjacent to the ciliary membrane. Microtubule-membrane bridges linked axonemal tubules to the ciliary membrane. The position, projection, and orientation of the axoneme were influenced by the structural organisation and mechanical properties of the matrix and frequently caused angulation of the ciliary shaft relative to the basal body. Located midway between the secretory apparatus and the extracellular matrix, primary cilia would appear ideally situated to mediate the necessry interaction between the cell and its surrounding environment prerequisite to the formation and maintenance of a functionally effective matrix. We propose that primary cilia in connective tissue cells could act as multifunctional, cellular cybernetic probes, receiving, transducing, and conducting a variety of extrinsic stimuli to the intracellular organelles responsible for effecting the appropriate homeostatic feedback response to changes in the extracellular microenvironment.
    Additional Material: 17 Ill.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 38 (1992), S. 1593-1608 
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A huge amount of data is collected by computer monitoring systems in the chemical process industry. Such tools as principal component analysis and partial least squares have been shown to be very effective in compressing this large volume of noisy correlated data into a subspace of much lower dimension than the original data set. Because most of what is eliminated is the collinearity of the original variables and the noise, the bulk of the information contained in the original data set is retained. The resulting low dimensional representation of the data set has been shown to be of great utility for process analysis and monitoring, as well as in selecting variables for control. These types of models can also be used directly in control system design. One way of approaching this is to use the loading matrices as compensators on the plant. Some advantages of using this approach as part of the overall control system design include automatic decoupling and efficient loop pairing, as well as natural handling of nonsquare systems and poorly conditioned systems.
    Additional Material: 20 Ill.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 139 (1989), S. 558-564 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Phosphatidic acid (PA) is synthesized as the result of the receptor-mediated response of platelets to physiologic agonists. The role of PA in platelet signal transduction, however, is largely unknown. We have examined the responses of platelets to 1-stearoyl-2-arachidonoyl phosphatidic acid (SAPA), the predominant molecular species of human platelet PA. SAPA alone causes platelet aggregation, and pretreatment of platelets with SAPA markedly enhances thrombin-induced aggregation and secretion. Addition of SAPA to intact human platelets causes rapid breakdown of phosphatidylinositol-4,5-bisphosphate (PIP2) and the generation of diacylglycerol and endogenous PA. These reactions are associated with mobilization of intracellular calcium and activation of protein kinase C. SAPA also stimulates the release of endogenous arachidonic acid and its conversion to thromboxane A2. Furthermore, platelet activation by SAPA is blocked by indomethacin, indicating that the actions of SAPA are mediated by cyclooxygenase products. These findings suggest that SAPA may play an important role as an endogenous positive feedback signal to amplify receptor-mediated activation of PIP2-specific phospholipase C in human platelets.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Zeitschrift für die chemische Industrie 81 (1969), S. 933-933 
    ISSN: 0044-8249
    Keywords: Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0730-2312
    Keywords: mutant repressors ; differential scanning calorimetry ; protein stability ; thermal denaturation ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The thermal denaturations of five revertant λ repressors containing single amino acid substitutions in their N-terminal domains have been studied by differential scanning calorimetry. Two substitutions slightly decrease stability, and the remaining three render the protein more stable than wild type. The Gly48 → Asn and Gly48 → Ser proteins are 4°C more stable than wild type. These two substitutions replace an α helical residue, and in each case a poor helix forming residue, glycine, is replaced by a residue with a higher helical propensity. We also present data showing that one revertant, Tyr22 → Phe, has reduced operator DNA binding affinity despite its enhanced stability.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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