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  • 1
    Electronic Resource
    Electronic Resource
    Contraction of Single Smooth Muscle Cells from Bufo marinus Stomach (1971)
    [s.l.] : Nature Publishing Group
    Nature 234 (1971), S. 351-352 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] A method for studying isolated smooth muscle cells would overcome many of the difficulties encountered with smooth muscle as a tissue. A technique for isolating living, beating heart cells using collagenase and trypsin has been developed by Vahouny et al.5, and we have modified it to isolate smooth ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/234351a0
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  • 2
    Electronic Resource
    Electronic Resource
    Evidence for perceptual masking of the discriminative morphine stimulus (1989)
    Springer
    Psychopharmacology 98 (1989), S. 212-221 
    Details
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Naltrexone ; Amphetamine ; Masking
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Morphine-amphetamine and morphine-naltrexone interactions were examined in three groups of White Carneaux pigeons (n=3), which were trained in a twochoice drug discrimination procedure under a FR-30 schedule of food reinforcement using 3.2 mg/kg morphine and saline as discriminative stimuli. Once stimulus control was acquired by these initial training stimuli, the training doses of morphine were gradually changed to 1.0 mg/kg for group A and to 10 mg/kg for group C. The three groups differed in the minimum dose required for stimulus control and the drugs to which the training stimulus generalized. Stimulus generalization to amphetamine was inversely related to training dose. Amphetamine potentiated the discriminative stimulus properties of morphine. Naltrexone blocked the discriminative stimulus properties of morphine to varying degrees, which appeared to be limited by the training dose and the rate-suppressing effects of naltrexone when administered alone. Challenging the morphine stimulus with amphetamine resulted in a qualitatively similar blockade. This blockade was a direct function of the morphine training dose. It is argued that MS-AMP interactions result in perceptual masking of the MS stimulus, which can be differentiated from pharmacological antagonism by NTX. Two other challenge drugs, ketamine, and sodium pentobarbital, did not alter stimulus control by morphine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00444694
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  • 3
    Electronic Resource
    Electronic Resource
    Effects of prior saline-morphine discrimination by pigeons on three-way discrimination including two morphine doses (1989)
    Springer
    Psychopharmacology 98 (1989), S. 222-230 
    Details
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Naltrexone ; Morphine ; Amphetamine ; Antagonism ; Pigeons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The discriminative stimulus properties of morphine sulfate (MS) and their alteration by naltrexone (NTX) and d-amphetamine (AMP) challenges were examined in a quantitative dose 1, dose 2, and saline (SAL) drug discrimination task utilizing 1.8 mg/kg MS, 10 mg/kg MS, and SAL as discriminative stimuli under a fixed-ratio 30 schedule of food-maintained behavior in two groups of White Carneaux pigeons. Group A (Gp A) (n=6) subjects (Ss) were initially experimentally-and drug-naive, whereas group B Ss (n=4) were originally trained in a two-choice MS versus SAL discrimination task, and had a long behavioral and drug history. Significant differences were found in (1) number of sessions to criterion (STC) (group B greater than group A); (2) group A Ss generalized both NTX and AMP to SAL, whereas group, B Ss generalized AMP to the low dose (1.8 mg/kg) MS stimulus; and (3) in drug interaction test sessions, the high dose MS stimulus (10 mg/kg) in group A was unmodified by a range of challenge AMP doses (0.32 to 3.2 mg/kg). In contrast, group B Ss exhibited a shift to the low dose or SAL-appropriate keys when the same high dose MS stimulus was challenged by moderate doses of AMP. Group A and group B were similar in their pattern and distribution of responses when tested with various doses of MS, and also when challenge tests of the high dose MS stimulus were made with NTX. Qualitative generalization tests with the opiate agonist methadone suggested that methadone was more potent than MS in producing the discriminative stimulus properties learned under the MS stimulus conditions. It is suggested that the three-choice dose 1, dose 2, SAL discrimination procedure is a viable model to test agonist and antagonist relationships.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00444695
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  • 4
    Electronic Resource
    Electronic Resource
    Increased sensitivity to rate-altering and discriminative stimulus effects of morphine following continuous exposure to naltrexone (1991)
    Springer
    Psychopharmacology 103 (1991), S. 67-73 
    Details
    ISSN: 1432-2072
    Keywords: Analgesia ; Behavior ; Drug discrimination ; Morphine ; Naltrexone ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two experiments evaluated whether termination of a continuous infusion of naltrexone altered sensitivity to the rate-suppressing or discriminative stimulus effects of morphine in rats. An 8-day infusion of saline or doses of 3, 10, or 18 mg/kg/day naltrexone did not alter rates of lever pressing maintained under fixed-ratio 30 schedules of food delivery. A dose of 10 mg/kg/day naltrexone produced insurmountable antagonism of the rate-suppressing and analgesic effects of morphine. The ED50 of morphine for rate suppression decreased by 2-fold 1 day after termination of the 8-day infusion of 10 or 18 mg/kg/day naltrexone. The ED50 of morphine returned to initial values within 8 days. Termination of infusion of either saline or 3 mg/kg/day naltrexone did not alter the ED50 of morphine. Changes in morphine stimulus control were evaluated in rats trained to discriminate saline and 3.2 mg/kg morphine under fixed-ratio 15 schedules of food delivery. The ED50 of morphine for stimulus control or rate suppression decreased by 2-fold 1 day after termination of an 8-day infusion of 18 mg/kg/day naltrexone. The ED50 of morphine for rate suppression returned to initial values within 3 days; that for stimulus control, within 5 days. Thus, termination of exposure to high doses of naltrexone produced brief changes in sensitivity to the rate-altering and discriminative stimulus effects of morphine that parallel reported changes in sensitivity to the analgesic and lethal effects of morphine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244076
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  • 5
    Electronic Resource
    Electronic Resource
    Tolerance to morphine stimulus control: role of morphine maintenance dose (1990)
    Springer
    Psychopharmacology 102 (1990), S. 59-67 
    Details
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Morphine ; Opioids ; Tolerance ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Experiments assessed the development of tolerance to morphine stimulus control during treatment with selected maintenance doses of morphine. Separate groups of rats were trained to discriminate saline and either 3.2 mg/kg or 5.6 mg/kg morphine under fixed-ratio schedules of food delivery. Dose-response functions for generalization of morphine stimulus control were determined before, during, and after repeated treatment with selected doses of morphine. Similar experiments were performed with repeated pentobarbital treatment in order to assess the pharmacological selectivity of tolerance. Repeated treatment with saline, 3.2 mg/kg morphine, or twice daily injections of 17.8 mg/kg pentobarbital produced no tolerance to morphine stimulus control. In contrast, treatment with daily injections of 10 mg/kg or twice daily injections of 10 or 17.8 mg/kg morphine produced a dose-dependent increase in the dose of morphine required for stimulus control. The magnitude of tolerance to morphine stimulus control varied directly with the maintenance dose of morphine and was slightly greater for a lower than a higher morphine training dose. Termination of repeated treatment was followed by a return to initial sensitivity, without additional training. Tolerance to morphine stimulus control was not necessarily accompanied by tolerance to its rate-suppressing effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245745
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  • 6
    Electronic Resource
    Electronic Resource
    Comparison of opioid agonists in maintaining responding and in suppressing morphine withdrawal in rhesus monkeys (1981)
    Springer
    Psychopharmacology 74 (1981), S. 329-335 
    Details
    ISSN: 1432-2072
    Keywords: Azidomorphine ; Codeine ; Fentanyl ; Heroin ; Ketobemidone ; Levorphanol ; Morphine ; Meperidine ; Methadone ; Propoxyphene ; Rhesus monkeys ; Drug-reinforced behavior ; Drug selfadministration ; Opioid agonists ; Opioid dependence ; Morphine withdrawal syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Sixteen opioid agonists were studied for their capacity both to maintain responding previously reinforced by codeine and to suppress the withdrawal syndrome induced by morphine deprivation in rhesus monkeys. All compounds, which included examples from each of the major chemical families of opioids, maintained responding at rates above those maintained by saline. There were differences among the compounds in the maximal response rates maintained, and large differences in their potencies in maintaining responding. In morphine-dependent monkeys, the abstinence signs that developed 14 h after the last morphine dose were suppressed completely by all of the compounds except codeine. There was a strong positive correlation (r=0.92) between the potency of a compound in maintaining drug-reinforced responding and the potency of the compound in suppressing the morphine withdrawal syndrome.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432741
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  • 7
    Electronic Resource
    Electronic Resource
    Antagonism of the discriminative effects of ethylketazocine, cyclazocine, and nalorphine in macaques (1984)
    Springer
    Psychopharmacology 84 (1984), S. 356-361 
    Details
    ISSN: 1432-2072
    Keywords: Drug discrimination ; ϰ opioids ; Ethylketazocine ; Cyclazocine ; Nalorphine ; Naltrexone ; Macaque monkeys
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract dl-Ethylketazocine (EKC, 0.01 mg/kg) and saline were established as discriminative stimuli for food-maintained responding in macaque monkeys. Thirty consecutive presses on a right or left lever were reinforced with food, contingent on whether EKC or saline were administered before the session. For tests of antagonism, naltrexone, or UM 979 [(l)-5,9-alpha-dimethyl-2-(3-furylmethyl)-2′-hydroxy-6,7-benzomorphan] was administered concomitantly with EKC,dl-cyclazocine, or nalorphine. Both antagonists blocked completely the EKC discriminative stimulus. The antagonism of the stimulus and rate-altering effects of EKC was surmountable, with considerable intersubject variability in the magnitude of the EKC dose increase required to overcome the blockade. Cyclazocine and nalophine, mixed agonist-antagonist opioids that share stimulus properties with EKC, were also susceptible to antagonism. Naltrexone antagonized completely the EKC stimulus effects of nalorphine; naltrexone and UM 979 antagonized completely the EKC stimulus effects of cyclazocine. Naltrexone antagonism of the cyclazocine stimulus was not surmountable, due to a lack of antagonism of the rate-decreasing effects of high cyclazocine doses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00555213
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  • 8
    Electronic Resource
    Electronic Resource
    In vivo apparent affinity and efficacy estimates for μ opiates in a rat tail-withdrawal assay (1998)
    Springer
    Psychopharmacology 136 (1998), S. 15-23 
    Details
    ISSN: 1432-2072
    Keywords: Key words Etonitazene ; Morphine ; Buprenorphine ; Etorphine ; GPA 1657 ; Affinity ; Efficacy ; Antinociception ; Clocinnamox
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Experiments in a rat tail-withdrawal assay tested the hypothesis that the magnitude and pattern of antagonism of μ opiate agonists by the insurmountable μ opioid antagonist clocinnamox are inversely related to agonist efficacy. In addition, these experiments examined whether this antagonism could be quantified to yield apparent affinity and efficacy estimates for the pharmacological characterization of five opiate agonists. Etonitazene, etorphine, morphine, buprenorphine, and GPA 1657 produced dose-dependent increases in tail-withdrawal latency until 100% maximum possible effect (%MPE) was obtained. Morphine required a higher dose of clocinnamox for a 50% reduction in maximal antinociceptive effect than did buprenorphine or GPA 1657. In contrast, no dose of clocinnamox tested decreased the%MPE for etonitazene or etorphine. These data suggest a rank order of relative efficacy of etonitazene ≥ etorphine 〉 morphine ≥ GPA 1657 ≥ buprenorphine. Similarly, numerical analysis of these data yielded the following apparent affinity and efficacy estimates: etonitazene (0.38 mg/kg, 128); etorphine (0.68 mg/kg, 125); morphine (50 mg/kg, 38), GPA 1657 (6.6, 39); and buprenorphine (0.042 mg/kg, 2.2). These data illustrate that in vivo affinity and efficacy estimates for a number of agonists are remarkably similar across different methods of analysis and are useful for drug classification.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050534
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  • 9
    Electronic Resource
    Electronic Resource
    Discriminative stimulus effects of two doses of fentanyl in rats: pharmacological selectivity and effect of training dose on agonist and antagonist effects of mu opioids (2000)
    Springer
    Psychopharmacology 148 (2000), S. 136-145 
    Details
    ISSN: 1432-2072
    Keywords: Key words Fentanyl ; mu opioids ; Drug discrimination ; Training dose ; pA2 analysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Discriminative stimulus effects of mu opioids vary systematically as a function of training dose. Differences among training doses may arise from multiple mechanisms. Objectives: In vivo apparent pA2 analyses were used to examine the contributions of opioid mechanisms to stimulus control by low and high training doses of the mu opioid fentanyl. Methods: Saline and one of two doses of fentanyl, administered s.c., were established as discriminative stimuli in two groups of rats (low training dose group: 0.01 mg/kg; high training dose group: 0.04 mg/kg). Generalization tests and in vivo apparent pA2 analyses were used to evaluate receptor mechanisms of stimulus control. Results: Fentanyl, etonitazene, methadone, and morphine evoked full fentanyl generalization in both groups but were more potent in the low-dose group. Spiradoline and d-amphetamine did not evoke generalization in either group. Naltrexone antagonized stimulus and rate-altering effects of fentanyl in both groups, with apparent pA2 values of 7.6 in the low-dose group and 7.5 in the high-dose group. Nalbuphine and nalorphine evoked full generalization in the low-dose group but less than 40% generalization in the high-dose group. In the high-dose group, nalbuphine and nalorphine antagonized the stimulus and rate-altering effects of fentanyl with apparent pA2 values of 5.3 and 6.1, respectively, demonstrating lower efficacy mu actions. Conclusions: Changes in fentanyl training dose preserved the mu opioid selectivity of stimulus control but altered the intensity of the transduced mu opioid stimulus required for generalization. These differences in intensity of the fentanyl stimulus determined whether low efficacy mu opioids would evoke or antagonize fentanyl generalization.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050035
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  • 10
    Electronic Resource
    Electronic Resource
    Naloxone effects on schedule-controlled behavior in morphine-pelleted rats (1979)
    Springer
    Psychopharmacology 62 (1979), S. 307-314 
    Details
    ISSN: 1432-2072
    Keywords: Morphine pellet ; Naloxone ; Schedule-controlled behaviors ; Precipitated abstinence ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of morphine pellet implantation and naloxone administration were examined in rats lever pressing under inter-response time schedules of food presentation. Subcutaneous implantation of a morphine pellet initially decreased lever-pressing rates. Tolerance to this effect developed within 3–4 days. Naloxone (0.25–1.0 mg/kg) decreased response rates in morphine-pelleted rats in a dose-dependent and time-dependent manner. All doses of naloxone severely decreased rates of lever pressing on days four to nine post-pellet. This rate-decreasing effect persisted 7–17 days for 0.25 mg/kg naloxone, 9–22 days for 0.50 mg/kg, and 13–28 days for 1.0 mg/kg. Decreases in response rate were due to an increased frequency of long pauses and not to marked shifts in the temporal patterning of those lever presses that did occur. Changes in response rate after naloxone were accompanied by body weight loss. Area values summarizing the naloxone-induced changes in response rate or body weight over time after pellet implantation increased as a function of naloxone dose. Naloxone (0.25–1.0 mg/kg) did not alter performance by placebo-pelleted rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00431963
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