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  • Life and Medical Sciences  (28)
  • Dopamine  (5)
  • Lignin model compounds  (5)
  • 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: 1432-072X
    Keywords: Phanerochaete chrysosporium ; Lignin model compounds ; β-Aryl ether dimers ; Metabolism ; Methoxyhydroquinone ; Alkyl-phenyl cleavage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The white rot basidiomycete Phanerochaete chrysosporium metabolized guaiacylglycol-β-guaiacyl ether (I) in high nitrogen, shaking and stationary cultures. 2-(o-Methoxyphenoxy) ethanol (X), 2-(o-methoxyphenoxy) acetic acid (IX) and methoxy-phydroquinone (MHQ) were identified as products of the metabolism of (I). P. chrysosporium also metabolized guaiacylglycerol-β-guaiacyl ether (IV) in high nitrogen stationary cultures. 2-(o-Methoxyphenoxy)-1,3 propanediol (XII) and 3-hydroxy, 2-(o-methoxy-phenyxy) propionic acid (XIV) were identified as products of the metabolism of (IV). Finally, P. chrysosporium metabolized α-deoxyguaiacylglycol-β-guaiacyl ether (VI) and α-deoxyguaiacylglycerol-β-guaiacyl ether (VII) in limiting nitrogen cultures. 2-(o-Methoxyphenoxy) ethanol (X) and 2-(o-methoxyphenoxy)-1,3 propanediol (XII) were identified as products of the metabolism of VI and VII respectively indicating α hydroxylation of those substrates with subsequent alkyl-phenyl bond cleavage. Metabolites were identified after comparison with chemically synthesized standards by GLC-mass spectrometry.
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  • 5
    ISSN: 1432-072X
    Keywords: Phanerochaete chrysosporium ; Lignin model compounds ; Lignin metabolism ; β-aryl ether dimers ; β-ether cleavage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The white rot basidiomycete Phanerochaete chrysosporium metabolized 4-ethoxy-3-methoxyphenyl-glycerol-β-guaiacyl ether (V) in low nitrogen, stationary cultures under which conditions the ligninolytic enzyme system is expressed. 4-Ethoxy-3-methoxyphenylglycerol XIII, guaicol and 4-ethoxy-3-methoxybenzyl alcohol (II) were isolated as metabolic products. Exogenously added XIII was rapidly converted to 4-ethoxy-3-methoxybenzyl alcohol indicating that it is an intermediate in the metabolism of V. P. chrysosporium also metabolized 1-(4′-ethoxy-3′-methoxyphenyl)-2-(2″-methoxyphenoxy)-3-hydroxypropane VI. The degradation pathway for this dimer also included initial β-ether cleavage and α-hydroxylation of the diol product 1-(4′-ethoxy-3′-methoxyphenyl) 2,3 dihydroxypropane (XI) to yield the triol XIII which was cleaved at the α, β bond to yield 4-ethoxy-3-methoxybenzyl alcohol. Finally P. chrysosporium also cleaved the dimer 1-(4′-ethoxy-3′-methoxyphenyl)-2-(2″-methoxyphenoxy)-1-hydroxypropane (VIII) at the β-ether linkage yielding 1-(4′-ethoxy-3′-methoxyphenyl) 1,2 dihydroxypropane (IX) which was subsequently cleaved at the α, β bond to yield II. All of the results indicate that oxidative β-ether cleavage is an important initial reaction in the metabolism of β-aryl ether lignin substructure dimeric compounds. Metabolities were identified after comparison with chemically synthesized standards by gas liquid chromatography-mass spectrometry.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-072X
    Keywords: Phanerochaete chrysosporium ; Vicinal diol cleavage ; Lignin model compounds ; Dihydroanisoin ; Anlsyl alcohol ; White rot basidiomycete ; Anisaldehyde ; Cytochrome P-450 ; Activated oxygen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The white rot basidiomycete Phanerochaete chrysosporium metabolized dihydroanisoin (1,2-dianisylethane-1,2 diol) in low nitrogen stationary cultures, conditions under which the ligninolytic system is expressed. Anisyl alcohol was isolated as a metabolic product indicating an initial diol bond cleavage of the substrate. Use of 3H-labeled dihydroanisoin (1,2-dianisylethane-1,2-diol-1,2 3H) indicated that the diol bond was cleaved directly, yielding anisyl aldehyde as the initial product. The metabolically stable ketol anisoin was shown not be an intermediate in the metabolism of dihydroanisoin. The diol cleavage reaction was dependent on the concentration of molecular oxygen but O2 could be replaced by H2O2 under some conditions. The cleavage reaction was inhibited by exogenously-added tyrosine2-Cu2+ complex (TCC). The appearance of the fungal diol cleavage system parallels the appearance of the ligninolytic system under a variety of physiological conditions. In addition, preincubation of ligninolytic cultures with 2.5 mM l-glutamate represses both the ligninolytic and the diol cleavage activities.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-072X
    Keywords: Phanerochaete chrysosporium ; Lignin model compounds ; β-aryl ether dimers ; Metabolism αβ cleavage ; Veratryl alcohol ; 4-ethoxy-3-methoxybenzyl alcohol ; Alkyl-phenyl cleavage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The white rot fungus Phanerochaete chrysosporium metabolized the lignin model compounds veratylglycerol-β-guaiacyl ether I and 4-ethoxy-3-methoxy-phenylglycerol-β-guaiacyl ether V in stationary culture under an atmosphere of 100% oxygen and under nitrogen limiting conditions. 2-(o-methoxyphenoxy)-ethanol VII was identified as a product of the metabolism of both substrates. Veratryl alcohol and 4-ethoxy-3-methoxybenzyl alcohol IV were identified as metabolites of I and V respectively. Metabolites were identified after comparison with chemically synthesized standards by mass spectrometry. These results indicate the existence of an enzyme system capable of directly cleaving the etherated dimers I and V at the α, β bond. The additional identification of 2-(o-methoxyphenoxy)-1,3 propanediol IX as a metabolic product indicates that cleavage of the alkyl-phenyl bond of these dimers or their metabolites also occurs.
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  • 8
    ISSN: 1432-072X
    Keywords: Phanerochaete chrysosporium ; Lignin model compounds ; Lignin degradation ; Diarylpropane ; α,β cleavage ; Anisyl alcohol ; Lignin ; Basidiomycete
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The white rot basidiomycete Phanerochaete chrysosporium metabolized 1-(3′,4′-diethoxyphenyl)-1,3(dihydroxy)-2-(4′'-methoxyphenyl)-propane (XII) in low nitrogen stationary cultures, conditions under which the ligninolytic enzyme system is expressed. 3,4-Diethoxybenzyl alcohol (IV), 1,2(dihydroxy)-1-(4′-methoxyphenyl)ethane (XX) and anisyl alcohol were isolated as metabolic products indicating an initial α, β bond cleavage of this dimer. Exogenously added XX was rapidly converted to anisyl alcohol, indicating that XX is an intermediate in the metabolism of XII. Fungal cleavage of the α, β bond of 1-(3′-4′-diethoxyphenyl)-1-(hydroxy)-2-(4′'-methoxyphenyl)ethane (XI) also occurred, indicating that a γ hydroxymethyl group is not a prerequisite for this reaction. P. chrysosporium also metabolized 1-(4′-ethoxy-3′-methoxyphenyl)-2,2(dihydroxy)-2-(4′'-methoxyphenyl)propane-1-ol (XIII). The major products of the degradation of this triol included 4-ethoxy-3-methoxybenzyl alcohol (III) and 2-hydroxy-1-(4′-methoxyphenyl)-1-oxoethane (XXI). The nature of the products formed indicates that this triol is also cleaved directly at the α,β bond. The significant difference in the nature of the products formed from the diaryl propane (XII) and the triol (XIII), however, suggests that XIII is not an intermediate in the major pathway for the degradation of XII. Metabolites were identified after comparison with chemically synthesized standards by GLC-mass spectrometry.
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  • 9
    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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  • 10
    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.
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