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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 97 (1989), S. 45-50 
    ISSN: 1432-2072
    Keywords: DRL ; Ethanol ; Operant behavior ; Rats ; Residual tolerance ; Tolerance ; Rate increases and decreases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Six male Sprague-Dawley rats were trained on a DRL-20 operant schedule for food presentation. When stable performance was established, they were exposed to an escalating regimen of daily ethanol administration (1.125–3.75 g/kg. IP). This dosing regimen continued until the maximally tolerable dose for each subject was reached. Tolerance loss then was monitored for approximately 6 months by periodic ethanol challenge doses (1.5 g/kg). Dose-effect curves (DECs) were obtained prior to (DEC-1), immediately after (DEC-2), and 6 months following termination of (DEC-3) the ethanol exposure. Rate-increasing effects (DEC-1) were noted at low doses (0.75 and 1.125 g/kg), with a higher dose (2.25 g/kg) resulting in a decreased rate of responding. Tolerance, following chronic ethanol exposure, developed to both the rate-increasing and ratedecreasing effects of ethanol (DEC-2). While some tolerance was lost within the 6 months following the daily ethanol exposure (DEC-3), a significant degree of tolerance was still indicated by most of the response measures. This duration of tolerance was considerably longer than that generally reported, and is probably attributable to persistent learned compensatory behavior and/or intermittent ethanol challenge tests.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Ethanol ; Tolerance ; Operant performance ; Delayed ethanol effect ; Drug-induced compensatory learning
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of pre-session and post-session daily ethanol injections on the development and loss of tolerance to ethanol's effects on fixed ratio operant performance in rats was assessed using a cumulative dosing procedure. Daily pre-session ethanol administration produced a greater decrease in ethanol sensitivity than did daily post-session ethanol. Both tolerance effects persisted for at least 1 month after the chronic injection phase. No changes in ethanol sensitivity were apparent in the saline control group and no changes in estimated blood ethanol levels were found after the chronic treatments. The post-session ethanol groups displayed a performance decrement during the initial segment of the chronic injection period, but improved significantly across the chronic phase. These data suggest that some delayed effect of ethanol initially impaired performance but that tolerance to this ethanol effect also occurred and probably contributed to the decline in ethanol sensitivity seen in these groups. Compensatory learning as the mechanism for tolerance development in the pre-session and post-session ethanol groups was supported by the finding of no change in ethanol sensitivity in rats exposed to comparable daily ethanol without any concurrent operant task on which the direct, immediate, or indirect, delayed ethanol effects could operate.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Methadone ; Cyclic AMP ; Tolerance ; Physical dependence ; Withdrawal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Laboratory and animal investigations have supported the hypothesis that levels of cyclic AMP are stable during tolerance to narcotic drugs and increased during withdrawal. In order to test this hypothesis, serial 24-h urinary excretion of cyclic AMP by long-term methadone addicts was determined during a period of stable methadone intake, a period of gradual withdrawal, and a period of acute withdrawal. Cyclic AMP excretion during stable methadone intake is identical to that of normal control subjects. Neither gradual nor acute withdrawal appears to affect the urinary excretion of cyclic AMP. These data agree with previous reports in the literature which suggest that cyclic AMP levels are not altered during tolerance to narcotics, but do not support the hypothesis that levels of the nucleotide might be increased during withdrawal.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2072
    Keywords: Behavioral tolerance ; Ethanol ; Operant behavior ; Rats ; Residual tolerance ; Tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Twelve male Sprague-Dawley rats, following training on one of two food-motivated operant schedules (Fixed-Ratio 30 or Variable Interval 30 s), were exposed to an escalating regimen of daily ethanol (1.125–3.0 g/kg, IP) administration. This increasing dose regimen continued until the maximally tolerable dose for each subject was reached. Tolerance was then monitored for approximately 6 months by periodic ethanol challenge doses (1.5 g/kg). Dose-effect curves (DECs) were obtained prior to chronic ethanol (DEC1), immediately after ethanol tolerance development (DEC2), and 6 months (DEC3) following termination of ethanol exposure. At DEC1, ethanol produced dose-dependent decreases in rate on both schedules with no significant schedule differences in ED50 (the dose effective at reducing the maximal response rate by one-half) values. Maximal tolerance was achieved in means of 46 and 55 days on the VI and FR schedules, respectively. Differences in rate of tolerance acquisition on the initial dose of the chronic regimen (1.125 g/kg) account for most of the difference in the overall rate of acquisition. Comparison of the ED50 data from DECs 1 and 2 indicated that daily ethanol exposure resulted in a 2-fold decrease in ethanol sensitivity (i.e., tolerance) on both operant schedules. The ED50 data from DECs 1 and 3 demonstrated a 1.7-fold decrease in ethanol potency on DEC3. This duration of tolerance was considerably longer than that generally reported, and possibly related to the extended ethanol exposure and the sensitivity of operant schedules to drug effects.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2072
    Keywords: Ethanol ; Operant performance ; Tolerance ; Intoxicated practice ; Compensatory behaviors ; Acute ethanol withdrawal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Acquisition and retention of tolerance to ethanol's rate-decreasing effects on operant performance were examined in rats which received a 52-day regimen of ethanol or saline injections prior to and/or after each daily session. Eight groups of rats differed on: (a) number of days with intoxicated practice (pre-session ethanol); (b) intermittent (spaced) or daily (massed) intoxicated practice; and (c) post-session ethanol or saline on nonintoxicated practice days. Massed practice groups were given their presession saline days prior to their pre-session ethanol days. Ethanol dose-effect tests were given prior to, during, and after the chronic injection regimen. Under both spaced and massed practice conditions, the magnitude of tolerance developed increased directly with the number of pre-session ethanol days, even when absolute ethanol exposure was constant. No group showed complete tolerance loss. The post-session ethanol supplements (a) facilitated tolerance development in spaced practice groups and tolerance loss in massed practice groups, (b) blocked ethanol's low dose rate-increasing effects, and (c) produced an acute withdrawal-like performance disruption the next day. The results suggest that both intoxicated practice and practice during acute ethanol withdrawal influence the acquisition and retention of compensatory behaviors during ethanol tolerance development.
    Type of Medium: Electronic Resource
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