Biomedical subjects
D C Bird
Publications and source records attributed to D C Bird.
Development and loss of tolerance to the effects of ethanol on DRL performance of rats.
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 rate-decreasing 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.
Tolerance to ethanol's disruptive effects on operant behavior in rats.
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.
Behavioral factors in development of tolerance to ethanol's effects.
Dose-effect analyses were used to monitor the development of tolerance for ethanol's effects on FR30 operant performance in rats under different conditions of chronic ethanol exposure: (a) pre-session ethanol injections (PRE) vs. post-session ethanol injections (POST) in Experiment 1; and (b) an ethanol liquid diet (ED) vs. a control diet (CD) in Experiment 2. The PRE and ED groups developed tolerance at the conclusion of the chronic regimens, which declined by six months but not to baseline levels. These data suggest that tolerance results from learned compensatory adjustments (through intoxicated practice) to ethanol's disruptive effects. The POST, but not the CD, group developed a progressively increasing degree of tolerance after several ethanol challenge tests. These results suggest that some threshold level of passive ethanol exposure in the POST group interacted with their limited intoxicated practice. Finally, the tolerance developed under intoxicated practice conditions did not appear to reflect a generalized tolerance to rate-reducing properties of drugs, changes in ethanol kinetics, or age-related changes.
Interactions between stimulants: effects on DRL performance and lethality in rats.
The Controlled Substances Act of 1970 drastically reduced the supply of amphetamines available to the public. It also inadvertently prompted the emergence of a new drug industry, namely the marketing of caffeine/phenylethylamine combinations packaged to look like many of the previously available amphetamine preparations. The findings of one recent experimental study corroborate anecdotal evidence that the interoceptive "high" produced by these look-alike stimulants mimics that produced by amphetamine. The present study was designed to further characterize the behavioral effects of caffeine/phenylethylamine combinations. The present findings suggest that adding ephedrine and phenylpropanolamine to caffeine markedly enhances the disruption of DRL performance, as well as the lethality of the drug. In addition, different patterns of interactions were obtained between amphetamine and caffeine versus the caffeine/ephedrine/phenylpropanolamine combination.
Schedule-controlled behavior as an index of the development and loss of ethanol tolerance in the rat.
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.
Effects of cortical, hypothalamic, and hippocampal lesions on chronic alcohol intake and preference in rats.
The effects of cortical, hippocampal, and suprachiasmatic (hypothalamic) lesions on forced alcohol consumption, alcohol preference and the distribution of alcohol intake throughout the day were examined in rats. Controls included by hypothalamic sham-operated and unoperated groups. Baseline water intake during light and dark and initial alcohol preference (10% alcohol versus water) were determined. All animals then were placed on a forced alcohol consumption regimen consisting of ad lib lab-chow and 10% ethanol in water. On the sixth day of each week during the alcoholization regimen, light and dark phase alcohol intake was assessed and on the seventh day of each week, a 24-hr, two-bottle alcohol preference test (10% ethanol) was given. After nine weeks on the forced alcohol regimen, all animals were given a seven day "withdrawal" period consisting of access to plain water and to 10% alcohol in water. Throughout both the forced alcoholization and withdrawal periods, the lesioned groups, especially the cortically lesioned group, displayed a significantly greater preference for the 10% alcohol solution than any of the control groups. Control and lesion groups did not differ significantly in their preference for a 5% alcohol solution or for a quinine solution, suggesting that simple taste threshold changes probably would not account for these data. The results are discussed in terms of the possibility that the brain lesions may have rendered the animals more sensitive to the "addictive" and/or reinforcing properties of ethanol.
Effect on bone growth of daily versus alternate-day corticosteroid administration: an experimental study.
Young rabbits that received large doses of corticosteroids on an alternate-day basis grew normally and showed muscle and bone turnover patterns indistinguishable from those of untreated animals. In contrast, the daily administration of corticosteroids profoundly affected the skeletal system: growth ceased, and there were marked narrowing and premature closure of the epiphyseal plates. Osteoporotic changes were present at 1 week and progressed during the next 9 weeks. Muscle atrophy occurred early in the course of treatment and was associated with increased muscle fat deposition. Thus, in this study, alternate-day administration of corticosteroids clearly lessened the corticosteroid side effects of growth retardation, osteoporosis, and muscle wasting.
Interocular transfer and type of motivation.
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