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  • Physical Chemistry  (7)
  • Dopamine  (5)
  • Chemical Engineering  (4)
  • 1
    Electronic Resource
    Electronic Resource
    Antagonism of amphetamine-induced disruption of latent inhibition in rats by haloperidol and ondansetron: Implications for a possible antipsychotic action of ondansetron (1994)
    Springer
    Psychopharmacology 114 (1994), S. 657-664 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF02244998
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  • 2
    Electronic Resource
    Electronic Resource
    Behavioural and neurochemical characteristics of phentermine and fenfluramine administered separately and as a mixture in rats (1997)
    Springer
    Psychopharmacology 131 (1997), S. 296-306 
    Details
    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
    URL: http://dx.doi.org/10.1007/s002130050296
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  • 3
    Electronic Resource
    Electronic Resource
    Effects of dopamine and serotonin-releasing agents on methamphetamine discrimination and self-administration in rats (1999)
    Springer
    Psychopharmacology 141 (1999), S. 287-296 
    Details
    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
    URL: http://dx.doi.org/10.1007/s002130050836
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  • 4
    Electronic Resource
    Electronic Resource
    Nicotine blocks latent inhibition in rats: evidence for a critical role of increased functional activity of dopamine in the mesolimbic system at conditioning rather than pre-exposure (1993)
    Springer
    Psychopharmacology 110 (1993), S. 187-192 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF02246971
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  • 5
    Electronic Resource
    Electronic Resource
    Dopaminergic mechanisms and cognitive deficit in schizophrenia (1979)
    Springer
    Psychopharmacology 63 (1979), S. 273-280 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00433561
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  • 6
    Electronic Resource
    Electronic Resource
    Hydrogen-bonding. Part 4. An analysis of solute hydrogen-bond basicity, in terms of complexation constants (log K), using F1 and F2 factors, the principal components of different kinds of basicityPart 3. M. H. Abraham, P. P. Duce, D. V. Prior, R. A. Schulz, J. J. Morris and P. J. Taylor, J. Chem. Soc. Faraday Trans. 1, 84, 865 (1988). (1989)
    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 2 (1989), S. 243-254 
    Details
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The principal components factors F1 and F2 in the equation \documentclass{article}\pagestyle{empty}\begin{document}$$ \log K = {\rm BDP}_0 + S_1 F_1 + S_2 F_2 $$\end{document} have been used to obtain S1 and S2 values for sets of hydrogen-bond bases against 32 reference acid/solvent systems. The constants S1 and S2 define an angle θ = tan-1 S2/S1 that is a measure of the electrostatic:covalent bonding ratio in the hydrogen-bond complex. It is shown that θ can vary from 53 (4-fluorophenol in CH2Cl2)to 86 degrees (Ph2NH in CCl4) depending on the reference acid and solvent. This variation in θ can lead to family dependent behaviour in plots of log K for bases against a given reference acid system vs log K for bases against another reference acid system, and precludes the construction of any general scale of hydrogen-bond basicity using log K values. Amongst a quite wide range of reference acid/solvent systems θ varies only from 64 to 73 degrees, and for bases against these reference systems a ‘reasonably general’ scale could be set up. Such a scale could be extended to bases against reference acid/solvent systems outside the 64-73 degree range provided that certain classes of base (e.g. pyridines, alkylamines) were excluded from the additional reference acid/solvent systems.
    Additional Material: 6 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/poc.610020307
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  • 7
    Electronic Resource
    Electronic Resource
    Hydrogen bonding. 31. Construction of a scale of solute effective or summation hydrogen-bond basicity (1993)
    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 6 (1993), S. 660-684 
    Details
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The β2H scale of solute hydrogen-bond basicity, formulated from 1:1 hydrogen-bond complexation constants in tetrachloromethane, has been used to set up a scale of effective or summation hydrogen-bond basicity, appropriate for the situation in which a solute is surrounded by solvent molecules. The method is based on the equation, \documentclass{article}\pagestyle{empty}\begin{document}$$ \log SP = c + rR_2 + s\pi _2^{\rm H} + a\sum {\alpha _2^{\rm H}} + b\sum {\beta _2 + vVx} $$\end{document} where SP is, in this work, a set of solute water-solvent partition coefficients in a given system. The explanatory variables are solute parameters as follows: R2 is an excess molar refraction, π2H is the solute dipolarity/polarizability, Σα2H and Σβ2 are the effective solute hydrogen-bond acidity and basicity and Vx is McGowan's characteristic volume. Various equations are established using β2H in the equation, and then amended β2H values are back-calculated and new Σβ2H values obtained. It is found that for most solutes, the effective basicity Σβ2H is invariant over the systems used to within an experimental error of around 0·03 units. About 350 Σβ2H values obtained from two or more experimental log P values are listed, together with values for homologous series and a number of singly determined values. For some specific solutes, such as sulphoxides, alkylanilines and alkylpyridines, Σβ2 is not constant, and an additional solute basicity denoted as Σβ2O is needed in order to deal with partitions from water to solvents that are partially miscible with water, such as isobutanol and octanol. Values of Σβ2O, and where possible Σβ2H also, are listed for 80 additional solutes.
    Additional Material: 17 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/poc.610061204
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  • 8
    Electronic Resource
    Electronic Resource
    Professor Robert W. Taft (1994)
    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 7 (1994), S. 655-656 
    Details
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/poc.610071202
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  • 9
    Electronic Resource
    Electronic Resource
    Hydrogen bonding. 38. Effect of solute structure and mobile phase composition on reversed-phase high-performance liquid chromatographic capacity factors (1994)
    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 7 (1994), S. 672-684 
    Details
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Reversed-phase HPLC capacity factors, as log k′, have been correlated through the LFER equation: \documentclass{article}\pagestyle{empty}\begin{document}$${\rm log k}^\prime = {\rm c} + {\rm rR}_2 + {\rm s\pi }_2^{\rm H} + {\rm a}\sum {\rm \beta }_2^0 + {\rm vV}_{\rm X}$$\end{document} where k′ is the capacity factor for a series of solutes in a given stationary phase-mobile phase system, and the explanatory variables are the solute descriptors: R2 an excess molar refraction, π2H the dipolarity/polarizability, Σα2H the overall hydrogen-bond acidity, Σβ20 the overall hydrogen-bond basicity and Vx the McGowan volume. This equation was applied to various C18 stationary phases with methanol-water, acetonitrile-water and tetrahydrofuran-water buffered mobile phases. The solute and mobile phase factors that influence log k′ values are set out, and a comparison is made between log k′ values and water-octanol partition coefficients.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/poc.610071205
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  • 10
    Electronic Resource
    Electronic Resource
    Hydrogen bonding. 39. The partition of solutes between water and various alcohols (1994)
    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 7 (1994), S. 712-716 
    Details
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The general solvation equation \documentclass{article}\pagestyle{empty}\begin{document}$${\rm logSP} = {\rm c} + {\rm rR}_2 + {\rm s\pi }_2^{\rm H} + {\rm a}\sum {\rm \beta }_2^{\rm H} + {\rm vV}_{\rm X}$$\end{document} was applied to the partition of solutes between water and isobutanol, pentanol, hexanol, octanol, decanol and oleyl alcohol. It is shown that the two main factors that influence partitioning are solute hydrogen-bond basicity Σβ2H and solute volume Vx. The b coefficient becomes steadily more negative along the above series of alcohols, showing that the alcoholic phases, which are all less acidic than water, become less and less acidic as the chain length increases, and the water content of the alcoholic phase decreases. The v coefficient, on the other hand, becomes gradually more positive, indicating that as the chain length increases and the water content decreases, the alcoholic phase becomes more and more hydrophobic. Of great significance is that for all six alcohols, the a coefficient is effectively zero, so that all alcoholic phases have the same basicity as bulk water, no matter what their water content is. It is suggested that, contrary to results of solvatochromic measurements, the alcohols have similar hydrogen-bond basicity to water.
    Additional Material: 2 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/poc.610071209
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