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  • Electronic Resource  (6)
  • Drug discrimination  (4)
  • Life and Medical Sciences  (2)
  • carbendazim  (2)
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  • Electronic Resource  (6)
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  • 1
    Electronic Resource
    Electronic Resource
    Discriminative stimulus properties of muscarinic agonists (1987)
    Springer
    Psychopharmacology 93 (1987), S. 139-145 
    Details
    ISSN: 1432-2072
    Keywords: Arecoline ; Pilocarpine ; Oxotremorine ; Acetylcholine ; Muscarinic agonist ; Drug discrimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a two-lever, food-reinforced drug-discrimination paradigm separate groups of rats were trained to discriminate either arecoline, pilocarpine or oxotremorine from saline. The discriminative cues of all three agonists were potently blocked by scopolamine, but only by 30–60 fold higher doses of methylscopolamine. The three agonists all suppressed overall response rate. These rate-suppressant effects were not blocked by scopolamine in doses which blocked the discriminative cues. In generalization tests, arecoline elicited selection of the drug-appropriate lever in all groups of trained animals. Pilocarpine was discriminated as drug by all pilocarpine-trained animals and by a majority of oxotremorine-trained animals, but was not significantly discriminated by the arecoline-trained group. Oxotremorine was discriminated by all oxotremorine-trained animals but only by some pilocarpine-trained animals, and was not significantly discriminated by the arecoline-trained group. Morphine, haloperidol, chlordiazepoxide, pentobarbital and nicotine were not generalized to any of the training drugs. The discriminative stimuli produced by the training drugs are therefore specific and exhibit properties indicative of an origin at central muscarinic receptors but may not be identical.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00179923
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacological characterization of the physostigmine stimulus in rats (1988)
    Springer
    Psychopharmacology 95 (1988), S. 553-555 
    Details
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Physostigmine ; M1 receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained to discriminate 0.10 mg/kg SC physostigmine from saline in a two-lever food-reinforced task. There was generalization to the acetylcholine esterase inhibitor THA as well as to the muscarinic receptor agonists arecoline, oxotremorine and RS 86, but not to neostigmine or nicotine. The physostigmine cue was blocked by SC scopolamine hydrobromide and by ICV pirenzepine, but not by scopolamine methylbromide or by mecamylamine. These antagonism studies suggest that the discriminative cue elicited by physostigmine might be mainly mediated by central M1 receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00172975
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  • 3
    Electronic Resource
    Electronic Resource
    Sex differences in the discriminative stimulus effects of m-chlorophenylpiperazine and ethanol withdrawal (2000)
    Springer
    Psychopharmacology 149 (2000), S. 170-175 
    Details
    ISSN: 1432-2072
    Keywords: Key words  m-Chlorophenylpiperazine ; Drug discrimination ; Ethanol withdrawal ; Anxiety ; 17β-estradiol ; Sex difference ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: The serotonergic system plays a role in regulation of anxiety and ethanol withdrawal (EW). Nevertheless, few studies have assessed sex differences in serotonergic effects on EW. Objectives: This study examined sex differences in the anxiogenic stimu-li induced by a serotonin (5-HT)1b/2 agonist, meta- chlorophenylpiperazine (mCPP), prior to ethanol and during EW. Methods: Gonadectomized or sham-operated adult male and female rats and 17β-estradiol (2.5 mg, 21-day release, s.c.) -replaced ovariectomized (OVX) rats were trained to discriminate mCPP (1.2 mg/kg, i.p.) from saline in a two-lever choice task for food. Latency to the first lever press and mCPP lever selection were measured following mCPP (0–1.2 mg/kg). Rats then received chronic ethanol-containing liquid diet (6.5%) for 10 days and were tested for mCPP lever selection 12 h and 36 h after removal of ethanol. Results: Fewer sham female and β-estradiol-replaced OVX rats selected the mCPP lever than male or OVX rats, and showed an increased initiation latency after mCPP injection. During EW (12 h and 36 h), fewer sham female and β-estradiol-replaced OVX rats responded on the mCPP-lever after saline injection as well as after mCPP challenge than male or OVX rats. Castration did not alter any response of male rats to mCPP. Conclusions: (1) mCPP discrimination is a useful measure of EW in male and female rats; and (2) sham female and β-estradiol-replaced OVX rats are less sensitive to the discriminative stimulus prior to and during EW, but more sensitive to impaired behavioral initiation induced by mCPP than male or OVX rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002139900353
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  • 4
    Electronic Resource
    Electronic Resource
    Characterization of the scopolamine stimulus in rats (1988)
    Springer
    Psychopharmacology 95 (1988), S. 195-199 
    Details
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Scopolamine cue ; Muscarinic agonists ; Muscarinic antagonists ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The discriminative stimulus properties of scopolamine, a potent antagonist at muscarinic receptors, were used for testing the discriminative effects of drugs known to act on cholinergic transmission. Rats were trained in a standard two-bar operant conditioning procedure with food as the reinforcer, according to a FR10 schedule. The training dose of scopolamine was progressively reduced from 0.25 mg/kg SC to the low dose of 0.062 mg/kg SC. Scopolarmine yielded an accurate discrimination in all the six rats tested. The generalization gradient resulted in an ED50 of 0.027 mg/kg. The scopolamine cue lasted for 1 h and was of central origin, since it was not mimicked by scopolamine methylbromide. The scopolamine stimulus generalized to atropine and trihexyphenidyl (respective ED50 values 2.20 and 0.21 mg/kg SC). Atropine depressed rate of responding, while trihexyphenidyl did not. Antagonism experiments with both direct agonists at the muscarinic receptor (arecoline and oxotremorine) and indirect agonists, i.e., inhibitors of the acetylcholine esterase [physostigmine and tetrahydroaminoacridine (THA)], led to inconsistent results. Increasing the doses of the agonists in order to block the scopolamine cue may be limited by their rate suppressant effect on responding. Based upon previously published results, it is suggested that the muscarinic agonist cue is more useful than the antagonist cue for investigating muscarinic transmission.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00174509
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  • 5
    Electronic Resource
    Electronic Resource
    Amino acid alterations in the benA (β-tubulin) gene of Aspergillus nidulans that confer benomyl resistance (1992)
    New York, NY : Wiley-Blackwell
    Cell Motility and the Cytoskeleton 22 (1992), S. 170-174 
    Details
    ISSN: 0886-1544
    Keywords: nocodazole ; carbendazim ; antimicrotubule agents ; thiabendazole ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: We report the cloning and sequencing of 18 mutant alleles of the benA, β-tubulin gene of Aspergillus nidulans that confer resistance to the benzimidazole antifungal, antimicrotubule compounds benomyl, carbendazim, nocodazole, and thia-bendazole. In 12 cases, amino acid 6 was changed from histidine to tyrosine or leucine. In four cases, amino acid 198 was changed from glutamic acid to aspartic acid, glutamine, or lysine. In two cases, amino acid 200 was altered from phenylalanine to tyrosine. These data, along with previous data indicating that amino acid 165 is involved in the binding of the R2 group of these compounds [Jung and Oakley, 1990: Cell Motil. Cytoskeleton 17:87-94], suggest that regions of β-tubulin containing amino acids 6, 165, and 198-200 interact to form the binding site of benzimidazole antimicrotubule agents. These results also suggest that the presence of phenylalanine at amino acid 200 contributes to the great sensitivity of many fungi to benzimidazole antimicrotubule agents. © 1992 Wiley-Liss, Inc.
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cm.970220304
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  • 6
    Electronic Resource
    Electronic Resource
    Identification of an amino acid substitution in the benA, β-tubulin gene of Aspergillus nidulans that confers thiabendazole resistance and benomyl supersensitivity (1990)
    New York, NY : Wiley-Blackwell
    Cell Motility and the Cytoskeleton 17 (1990), S. 87-94 
    Details
    ISSN: 0886-1544
    Keywords: benzimidazole ; anti-microtubule agents ; carbendazim ; nocodazole ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: We are using molecular genetic techniques to identify sites of interaction β-tubulin with benzimidizole anti-microtubule agents. We have developed a marker-rescue technique for cloning mutant alleles of the benA, β-tubulin gene of Aspergillus nidulans and have used the technique to clone two mutant benA alleles, benA16 and benA19. These are the only A. nidulans alleles known to confer resistance to the benzimidazole antimicrotubule agent thiabendazole and supersensitivity to other benzimidazole antimicrotubule agents including benomyl and its active breakdown product, carbendazim. benA16 has been shown, moreover, to reduce thiabendazole binding to β-tubulin. We have sequenced the two mutant alleles and have found that they carry different nucleotide changes that cause the same single amino acid substitution, valine for alanine at amino acid 165. Since thiabendazole and carbendazim differ at only one side chain, the R2 group, we conclude that the region around amino acid 165 is involved in the binding of the R2 group of benzimidazole antimicrotubule agents to β-tubulin.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cm.970170204
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