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  • 1
    Electronic Resource
    Electronic Resource
    Associative control of tolerance to the sedative and hypothermic effects of chlordiazepoxide (1985)
    Springer
    Psychopharmacology 86 (1985), S. 487-493 
    Details
    ISSN: 1432-2072
    Keywords: Conditioning ; Tolerance ; Chlordiazepoxide ; Sedation ; Hypothermia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pavlovian control of tolerance to the sedative and hypothermic effects of chlordiazepoxide (CDP) was demonstrated in two experiments. In Experiment I, drug-experienced rats were repeatedly treated with CDP (30 mg/kg) in one environment (CS+); on alternate days, they were given saline injections in a different environment (CS-). Duration of sleeping and inactivity were used as measures of sedation. A comparable conditioning procedure was used in Experiment II, but tolerance to the hypothermic effect of CDP was the dependent measure. During tolerance testing, rats from both Experiments I and II were given CDP in one of three environments, CS+, CS-, or a novel environment (CSnov). In Experiment I, rats were equally tolerant in all three test environments when duration of sleep was assessed. However, when inactivity was used as the measure of tolerance, rats showed tolerance in CS+ and CS-, and significantly less tolerance in CSnov. Drug-naive controls showed similar nontolerant responses to CDP in all environments, thus ruling out the possibility that the effect of sedation was mediated nonassociatively. In Experiment II, drug-experienced rats showed tolerance to CDP-induced hypothermia in CS+ and CS- but less tolerance in CSnov. A compensatory hyperthermia was observed when these rats were given saline in CS+. There was some evidence for a generalization gradient in the conditional control of tolerance in both experiments.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427914
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  • 2
    Electronic Resource
    Electronic Resource
    Acquisition of tolerance to alcohol-induced memory deficits in humans (1981)
    Springer
    Psychopharmacology 73 (1981), S. 176-179 
    Details
    ISSN: 1432-2072
    Keywords: Tolerance ; Alcohol ; Memory ; Alcoholics ; Neuropsychological functioning
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The evidence on tolerance to the effects of alcohol on memory functions is conflicting. Comparisons of populations differing in drinking history (alcoholics versus normal subjects) provide clear evidence of tolerance to alcohol's effect in many indices of psychomotor performance, but not to impairment of recall by alcohol. In contrast, acute or intrasessional tolerance to alcohol's effect on memory has been demonstrated. In the context of a larger experiment on the acquisition of tolerance in nonalcoholic subjects an assessment of the effects of repeated daily exposure to alcohol on verbal recall was possible. The experimental design incorporated 3 baseline days prior to the administration of alcohol, 10 consecutive days of exposure to alcohol (1.0 g/kg test dose, with supplementary 0.9 g/kg after testing) and 3 further days on which no alcohol was administered. Data on seven subjects were available for the memory task, which consisted of free recall of lists of 24 words grouped into six categories of four words each. On each day, recall was assessed both prior to and following the administration of a control beverage or alcohol. Alcohol reduced the number of words recalled (P〈0.005) and, with repeated exposure, the impairment of recall by alcohol was reduced (P〈0.005) providing evidence of tolerance. The effect of alcohol and the development of tolerance were reflected primarily in the number of categories represented in recall, whereas the number of words recalled per category was relatively unaffected by alcohol. It was conjectured that previous failures to find tolerance to alcohol's effect on memory may reflect deficits in neuropsychologic functioning resulting from years of heavy drinking.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00429213
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  • 3
    Electronic Resource
    Electronic Resource
    Pavlovian control of cross-tolerance between pentobarbital and ethanol (1981)
    Springer
    Psychopharmacology 74 (1981), S. 54-57 
    Details
    ISSN: 1432-2072
    Keywords: Cross-tolerance ; Ethanol ; Pavlovian conditioning ; Pentobarbital ; Tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tolerance to several effects of a number of drugs has been shown to depend on Pavlovian conditioning processes. Experiment I extended the compensatory conditioning model (Siegel 1975) to tolerance to the hypothermic effect of pentobarbital (30 mg/kg). In Experiment I, rats that acquired hypothermic tolerance in one environment did not display tolerance when tested in an environment not previously associated with drug administration. In Experiment II, rats were made tolerant to the hypothermic effect of pentobarbital (30 mg/kg) and tested for cross-tolerance to ethanol (2.5 g/kg). Cross-tolerance was observed, but it was significantly reduced if the test was in an environment different from the one in which tolerance to pentobarbital was originally acquired. Thus, the compensatory conditioning model accounts for at least part of the tolerance and crosstolerance to the thermic effects of alcohol and pentobarbital. The physiological processes in the CNS underlying tolerance and cross-tolerance for these drugs, therefore, are controlled by associative processes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00431757
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  • 4
    Electronic Resource
    Electronic Resource
    Alcohol is an effective cue in the conditional control of tolerance to alcohol (1984)
    Springer
    Psychopharmacology 83 (1984), S. 159-162 
    Details
    ISSN: 1432-2072
    Keywords: Conditioning ; Tolerance ; Alcohol ; Temperature ; Conditional stimuls
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To assess the effectiveness of a pharmacological cue as a conditional stimulus in the Pavlovian model of drug tolerance, two groups of Wistar rats received equal numbers of IP injections of a low and a high dose of alcohol. One group (Paired) received a low dose (0.8 g/kg) of alcohol followed 60 min later by the high dose (2.5 g/kg). Another group (Unpaired) received the low and high doses on an unpaired basis. When tested for tolerance to the hypothermic effect of the high dose of alcohol, only the Paired group showed tolerance, and only if the low dose preceded the high. When a saline injection preceded the high dose injection, the Paired group showed a loss of tolerance. The Paired group also showed a compensatory hyperthermia following the low dose injection. Animals from the Paired group that received repeated administrations of the low dose followed by saline, showed a significant extinction effect as compared with animals that received repeated saline injections only. These findings support the Pavlovian model of conditional tolerance, extending the realm of effective conditional stimuli to include a low dose of a drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00429726
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  • 5
    Electronic Resource
    Electronic Resource
    Associative factors in drug pretreatment effects on gustatory conditioning: Cross-drug effects (1979)
    Springer
    Psychopharmacology 64 (1979), S. 209-213 
    Details
    ISSN: 1432-2072
    Keywords: Gustatory conditioning ; Pretreatment effects ; Tolerance ; Amphetamine ; Morphine ; Compensatory conditioning
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pretreatment effect (PE) in gustatory avoidance conditioning refers to the fact that pretreatment with a variety of pharmacological agents subsequently reduces the ability of the same agents to induce gustatory aversion. Explanations of this phenomenon emphasize either tolerance or associative interference. Any explanation of the phenomenon must also account for the present findings which demonstrate the PE when agents of pretreatment and conditioning were pharmacologically dissimilar. Rats were pretreated with d-amphetamine and tested for acquisition of an aversion to saccharin conditioned by amphetamine or morphine. The PE was obtained regardless of the drug used in conditioning. An associative manipulation involving nonreinforced presentation of the drug administration cues (i.e., injections followed by saline instead of drug), that attenuated the PE when pretreatment and conditioning were with amphetamine, was also effective when the pretreatment agent was amphetamine and the conditioning agent was morphine. The findings were interpreted within a framework of compensatory conditioning of a general physiological mechanism common to all gustatory avoidance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00496064
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  • 6
    Electronic Resource
    Electronic Resource
    “Paradoxical” analgesia induced by naloxone and naltrexone (1988)
    Springer
    Psychopharmacology 96 (1988), S. 36-39 
    Details
    ISSN: 1432-2072
    Keywords: Analgesia ; Pain ; Naloxone ; Naltrexone ; Opiates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Analgesic effects of pellet implantation of the opiate antagonists naloxone and naltrexone and of chronic administration of naloxone by subcutaneous injection were examined. Rats were implanted with a slow-release pellet containing 10 mg naloxone or 10 mg naltrexone and tested for paw-lick latency on a hotplate apparatus. Controls were implanted with placebo pellets or given saline injections as appropriate. There were five test trials at intervals up to 72 h after implantation of naloxone and up to 120 h after the implantation of naltrexone. In a separate experiment, 5 mg/kg naloxone was injected; there were single trials on 5 consecutive days. All drug-treated animals displayed clear and substantial analgesia by their second test trial. This “paradoxical” analgesia was gradually reversed in the pellet-implant groups as tissue levels of the antagonists declined, but increased progressively with each trial involving injections. It was hypothesized that blockade of endogenous opiates by antagonists resulted in a form of “super-pain” on the hotplate, which in turn activated a normally redundant “backup” analgesic system. The results with naloxone injections show that unlike opiate-mediated analgesia, this hypothetical system is resistant to tolerance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02431530
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  • 7
    Electronic Resource
    Electronic Resource
    Drug deprivation and reinforcement by diazepam in a dependent population (1987)
    Springer
    Psychopharmacology 91 (1987), S. 154-160 
    Details
    ISSN: 1432-2072
    Keywords: Benzodiazepines ; Dependence ; Treatment ; Reinforcement ; Self-administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Individuals who were using therapeutic doses (approximately 15 mg diazepam or its equivalent daily) of a benzodiazepine persistently and wished to attempt to stop were recruited into a study offering a medically supported outpatient behavioral treatment with a goal of abstinence. All subjects received the same behavioral treatment that emphasized the development of strategies for coping with abstinence and alternatives to benzodiazepines as a coping mechanism. The goal of abstinence was to be achieved within approximately 8 weeks by means of gradual tapering of the daily dose. Some subjects (Group D, n=23) were randomly assigned to a condition in which their dose was to be tapered on a regime of active diazepam. Others (Group P, n=19) were switched to placebo at the first treatment session and “tapered” from this pharmacologically inert substitute for diazepam. Supplies of tablets of each preparation were provided by the experimenters, and subjects were specifically requested to use only those tablets. The principal dependent variable was “supplementation”, or use of a benzodiazepine other than that specifically authorized by the therapist. Supplementation was detected by measures of plasma benzodiazepine levels as compared to levels predicted if there had been strict compliance with the therapeutic regime. These comparsions were made by two expert judges who were blind to the subjects' experimental assignment. Self-report of supplementation was also obtained. Plasma level determinations indicated a significantly greater frequency of supplementation (84% versus 33% of subjects) for subjects in Group P. This was corroborated by self-report. These data support the assertion that dependence on low doses of benzodiazepines has a pharmacologic basis, and that there is a causal relationship between deprivation of a benzodiazepine and its self-administration in dependent persons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00217055
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  • 8
    Electronic Resource
    Electronic Resource
    Tolerance to morphine analgesia is reduced by the novel addition or omission of an alcohol cue (1988)
    Springer
    Psychopharmacology 94 (1988), S. 412-416 
    Details
    ISSN: 1432-2072
    Keywords: Drug cues ; Morphine ; Alcohol ; Tolerance ; External inhibition ; Conditioning
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A recent study demonstrated that ethanol tolerance was reduced by the presentation of a novel extraneous stimulus at the time of test. In Pavlovian terms, this phenomenon is known as external inhibition. The present study sought to determine whether a drug cue could act as an external inhibitor of tolerance. Theoretically, either the occurrence of an unexpected stimulus or the nonoccurrence of an expected one can operate to disrupt already established conditioned responses. This prediction was assessed in the present study by the novel presentation or the novel omission of a drug cue at test. Two groups of rats were made completely tolerant to the analgesic effects of morphine. During tolerance acquisition the groups were treated identically except that one group always received a dose of alcohol 15 min following morphine. At test, animals experienced either the novel introduction or the novel omission of the alcohol cue. Both manipulations led to a reduction of morphine analgesia. Beyond their theoretical importance, these results have clinical implications in view of the frequency of multiple concurrent drug abuse.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00174699
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  • 9
    Electronic Resource
    Electronic Resource
    An associative analysis of pretreatment effects in gustatory conditioning by amphetamine (1979)
    Springer
    Psychopharmacology 64 (1979), S. 201-207 
    Details
    ISSN: 1432-2072
    Keywords: Gustatory conditioning ; Pretreatment effects ; Tolerance ; Amphetamine ; Associative blocking
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Various attempts have been made to account for the fact that pertreatment with some pharmacological agents reduces the ability of such agents to induce conditioned aversion to a flavor. One explanation, based on the concept of tolerance, suggests that pretreatment is effective because it renders the animal less sensitive to direct effects of a given dose of the agent. A second explanation emphasizes the possibility that procedural consequences of pretreatment interfere with associability of flavor and drug effect during conditioning. The second explanation was tested in two experiments. In Experiment I nonreinforced presentations of drug administration cues completely reversed the attenuating effects of amphetamine pretreatment on gustatory conditioning by amphetamine. This finding was replicated and extended in the second experiment which was also designed to eliminate an alternative nonassociative explanation for the results. The principle of associative blocking may explain the effect of pretreatment on subsequent gustatory conditioning by drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00496063
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  • 10
    Electronic Resource
    Electronic Resource
    Role of central versus peripheral opioid receptors in analgesia induced by repeated administration of opioid antagonists (1991)
    Springer
    Psychopharmacology 104 (1991), S. 164-166 
    Details
    ISSN: 1432-2072
    Keywords: Quaternary naltrexone ; CNS opioid receptors ; Analgesia ; Hot plate testing ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Although analgesia induced by blockade of opioid receptors has been well established, it is still unknown whether its development is mediated by the blockade of centrally located opioid receptors. Therefore, rats were treated with either systemically or ICV applied naloxone or quaternary naltrexone (QN), an opioid antagonist that does not easily penetrate the blood-brain barrier. Following antagonist administration, each animal was tested for paw lick latency on a 51° C hot plate. Hot plate testing and drug injections were carried out for 4 consecutive days. Rats treated with ICV microinjections of QN or naloxone displayed paw lick latencies that were significantly longer than those observed in control animals. In contrast, rats treated with SC injections of QN did not show any increase in paw lick latency, whereas rats treated with SC injections of naloxone displayed paw lick latencies that were significantly longer than those of control rats. These results are consistent with the hypothesis that the blockade of central opioid receptors underlies the development of an analgesic response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244172
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