Biomedical subjects

A Poling

Publications and source records attributed to A Poling.

At least 55 records · Page 3Linked to original sources

PubMed1988

Effects of mephenytoin on schedule-controlled responding in the pigeon.

Acute and chronic effects of mephenytoin (30-360 mg/kg) were examined in pigeons responding under a multiple fixed-ratio 50 fixed-interval 90-sec schedule of food delivery. The highest dose administered acutely (240 mg/kg) produced substantial reductions in rate of responding under both components of the multiple schedule; the effects of other doses were small and inconsistent. With chronic exposure tolerance appeared to develop to the rate-decreasing effects of the drug.

Animals↗

PubMed1988

Effects of mephenytoin and methsuximide on the reaction time of pigeons.

Although antiepilepsy drugs are used clinically, their behavioral effects are poorly understood. The present study examined the effects of mephenytoin and methsuximide, two antiepilepsy medications, on the reaction times of pigeons. Pigeons were trained to depress and hold a foot treadle until a stimulus change occurred. Releases within 2 sec of the stimulus change were reinforced with access to mixed grain; premature releases or releases occurring after the 2-sec limited hold were not reinforced. Mephenytoin (40, 60, 80, 120, and 160 mg/kg) and methsuximide (25, 50, 75, and 100 mg/kg) produced generally dose-dependent increases in median reaction times and decreases in percent responses that were reinforced. The present procedure has not previously been used with pigeons and is a promising technique for the study of reaction time with this species.

Animals↗

PubMed1988

Failure of the partial inverse benzodiazepine agonist Ro15-4513 to block the lethal effects of ethanol in rats.

The partial inverse benzodiazepine agonist Ro15-4513 has been found to antagonize some of the behavioral and physiological effects of low to moderate doses of ethanol. In the present study, pretreating rats with Ro15-4513 (1, 3, 10, and 30 mg/kg) at doses equal to or greater than those used in prior investigations failed to block the lethal effects of intraperitoneal injections of ethanol at a dose of 5.4 g/kg. These results suggest that the lethal actions of ethanol may involve a mechanism that is not blocked by Ro15-4513, which is known to selectively antagonize ethanol-stimulated chloride uptake via the GABA-coupled chloride ion channel.

Alcoholic Intoxication↗

PubMed1988

Evaluation of a procedure to measure the time course of a drug's behavioral action.

The utility of a novel procedure to examine a drug's time course of behavioral action was evaluated. Time- and dose-effect relations for the antiepilepsy drug methsuximide were determined in pigeons during 12-hr overnight sessions through the use of a multiple variable-interval 60-sec extinction (mult VI EXT) schedule of food delivery. The VI 60-sec components were programmed for the first 10 min of each hour and were followed by 50-min EXT components. Methsuximide produced dose-dependent decreases in rate of responding; the higher the dose, the longer the duration of effect. The present procedure appears to be useful for determining effective presession injection intervals and time-effect relations.

Animals↗

PubMed1988

Self-control in mentally retarded adolescents: choice as a function of amount and delay of reinforcement.

Three severely mentally retarded adolescents were studied under discrete-trial procedures in which a choice was arranged between edible reinforcers that differed in magnitude and, in some conditions, delay. In the absence of delays the larger reinforcer was consistently chosen. Under conditions in which the smaller reinforcer was not delayed, increasing the delay to delivery of the larger reinforcer decreased the percentage of trials in which that reinforcer was chosen. All subjects directed the majority of choice responses to the smaller reinforcer when the larger reinforcer was sufficiently delayed, although the value at which this occurred differed across subjects. Under conditions in which the larger reinforcer initially was sufficiently delayed to result in preference for the smaller one, progressively increasing in 5-s increments the delay to both reinforcers increased percentage of trials with the larger reinforcer chosen. At sufficiently long delays, 2 of the subjects consistently chose the larger, but more delayed, reinforcer, and the 3rd subject chose that reinforcer on half of the trials. These results are consistent with the findings of prior studies in which adult humans responded to terminate noise and pigeons responded to produce food.

Adolescent↗

PubMed1987

Discriminative stimulus properties of ethosuximide in the pigeon.

After initial exposure to 80 mg/kg, pigeons trained on a two-key drug discrimination procedure rapidly learned to discriminate 120 mg/kg ethosuximide from saline. When 40-160 mg/kg doses of ethosuximide were administered during generalization tests, the percentage of responses directed to the ethosuximide-appropriate key varied directly with dose. Time-effect determinations revealed that the discriminable properties of ethosuximide were evident as early as 15 min after, and as late as 2 h after, intramuscular injection. The discriminative stimulus properties of ethosuximide failed to generalize to the anticonvulsant compounds clonazepam (0.5-4 mg/kg), methsuximide (25-200 mg/kg), and phenytoin (5-15 mg/kg). Generalization was apparent with certain doses of primidone (250, 300 mg/kg) and mephenytoin (80, 160, 240 mg/kg). The concomitant administration of pentylenetetrazol (5, 10, 20 mg/kg) partially blocked the discriminable properties of the training dose of ethosuximide.

Animals↗

PubMed1987

Effects of methsuximide and mephenytoin on the behavior of pigeons under a repeated acquisition procedure.

Learning impairment is a potentially serious side effect of antiepilepsy medications. The present study investigated the effects of methsuximide and mephenytoin on learning in pigeons performing under a repeated acquisition procedure. Given acutely, methsuximide (25, 50, 75, and 100 mg/kg) and mephenytoin (60, 120, and 240 mg/kg) produced generally dose-dependent decreases in rates of responding. High doses of each drug increased overall errors; a within-session analysis of error distributions also indicated learning impairment.

Animals↗

PubMed1987

Choice between sequences of fixed-ratio schedules: effects of ratio values and probability of food delivery.

Pigeons were exposed to schedules of food delivery that consisted of two sequential fixed ratios. When alternative sequences provided two food deliveries per 50 responses, the schedule with the shorter initial fixed-ratio value was consistently preferred. Progressively reducing from 1.0 to .25 the probability of food delivery following completion of the second fixed ratio of the sequence with the shorter initial fixed ratio did not reduce preference for this sequence. Moreover, the sequence with the shorter initial fixed ratio also was preferred when the probability of food delivery following completion of the initial ratio in that sequence was progressively reduced from 1.0 to .5, although preference shifted to the alternative when the probability was reduced to 0. These findings suggest that the length of the initial fixed ratio was a primary determinant of choice. Subsequent manipulations demonstrated, however, that when the initial fixed ratios of the two alternatives were equal, changes in the ratio value and probability of food delivery following completion of the second fixed ratio lawfully affected choice.

Animals↗

PubMed1986

Chronic effects of ethosuximide, phenytoin, clonazepam, and valproic acid on the delayed-matching-to-sample performance of pigeons.

Acute and chronic effects of ethosuximide (40, 80, and 120 mg/kg), phenytoin (2.5, 5, and 7.5 mg/kg), clonazepam (0.25, 0.5, and 0.75 mg/kg), and valproic acid (40, 80, and 120 mg/kg) were examined in pigeons performing under a delayed-matching-to-sample procedure. Acute administration of clonazepam or valproic acid produced generally dose-dependent decreases in accuracy; over 50 sessions of daily exposure, complete or nearly complete tolerance developed to the accuracy-reducing effects of these drugs. Whether administered acutely or chronically, ethosuximide and phenytoin failed to affect accuracy. When given acutely, all drugs typically reduced rate of responding to the sample stimulus. A degree of tolerance appeared to develop to the rate-decreasing effects of all of the drugs tested.

Animals↗

PubMed1986

Effects of clonazepam and ethosuximide on the responding of pigeons under a fixed-consecutive-number schedule with and without an external discriminative stimulus.

The effects of the anticonvulsant drugs clonazepam and ethosuximide were examined in pigeons performing under a fixed-consecutive-number schedule with and without an added external discriminative stimulus. Under these schedules, food was delivered whenever subjects responded between and 8 and 12 times on one response key (work key), and then responded once on a second response key (reinforcement key). For one group, an external discriminative stimulus signalled completion of the response requirement on the work key, while no stimulus change was programmed for the other group. Clonazepam (0.06-0.75 mg/kg) produced dose-dependent decreases in percentage of reinforced runs and rate of responding for both groups. The magnitude of the accuracy-decreasing effect was generally greater in the group without the external discriminative stimulus. For this group, the higher doses of clonazepam produced pronounced increases in switching to the reinforcement key before completing the minimum requirement of eight consecutive responses on the work key. No consistent patterns of errors were evident for the subjects with the added external discriminative stimulus. Although ethosuximide (20-160 mg/kg) produced dose-dependent decreases in rate of responding, it had little effect on the percentage of reinforced runs or the run length distributions. These findings are consistent with previous reports indicating that clonazepam, but not ethosuximide, substantially disrupts performance under operant tasks requiring conditional discriminations. These data also suggest that the addition of an external discrimination stimulus attenuates the disruptive behavioral effects of clonazepam.

Animals↗

PubMed1986

Effects of phenobarbital in combination with phenytoin or valproic acid on the delayed-matching-to-sample performance of pigeons.

The present study examined the effects of phenobarbital (5, 10, 20, and 40 mg/kg), phenytoin (2.5, 5, 7.5, and 15 mg/kg), and valproic acid (40, 60, 80, and 120 mg/kg), and those of phenobarbital (10 and 20 mg/kg) in combination with phenytoin (2.5, 5, and 7.5 mg/kg) or valproic acid (40, 60, and 80 mg/kg), on the delayed-matching-to-sample performance of pigeons. In general, high doses of each individual drug reduced accuracy. Drug combinations also reduced accuracy relative to control values. Reductions in accuracy produced by drug combinations were very similar in magnitude to those predicted by a response-addition model of drug interaction.

Animals↗

PubMed1986

Chronic effects of clonazepam, phenytoin, ethosuximide, and valproic acid on learning in pigeons as assayed by a repeated acquisition procedure.

The acute and chronic effects of the antiepileptic drugs clonazepam (0.06, 0.13, and 0.25 mg/kg), phenytoin (2.5, 5, and 7.5 mg/kg), ethosuximide (40, 80, and 120 mg/kg), and valproic acid (40, 80, and 120 mg/kg) were evaluated in pigeons responding under a repeated acquisition procedure. At certain doses, acute administrations of all drugs impaired learning (i.e., increased errors) and reduced rate of responding. Appreciable tolerance developed to these effects with chronic exposure, although the physiological mechanism responsible for this outcome is unknown.

Animals↗

PubMed1986

Effects of anticonvulsant drugs under automaintenance and negative automaintenance procedures.

The behavioral effects of phenytoin, phenobarbital, clonazepam, valproic acid, and ethosuximide were evaluated in food-deprived pigeons performing under automaintenance and negative automaintenance procedures. Under the automaintenance procedure, brief periods of key illumination were followed by food delivery without regard to the subject's behavior. In most instances, when drugs were not given this procedure engendered high rates of keypecking during almost all key illuminations (trials). Acute administrations of phenytoin (10-20 mg/kg), valproic acid (40-120 mg/kg), and ethosuximide (40-120 mg/kg) produced generally dose-dependent decreases in percent trials with a response and rate of responding. Although phenobarbital (30-60 mg/kg) and clonazepam (2.5-7.5 mg/kg) produced little obvious effect on percent trials with a response, these drugs generally increased rate of responding. Under the negative automaintenance procedure, food delivery followed only key illuminations during which keypecking did not occur. Keypecking occurred at a low rate under this procedure, with no responses occurring during the majority of key illuminations. Thus, this procedure appeared to involve responding elicited by respondent conditioning but suppressed by the response-dependent omission of food. Across the same dose ranges evaluated under the automaintenance procedure, clonazepam and phenobarbital generally increased percent trials with a response and rate of responding in dose-dependent fashion. Phenytoin similarly increased percent trials with a response but had little consistent effect on rate of responding. Ethosuximide and valproic acid failed to affect responding under this procedure.

Animals↗

PubMed1986

Modulation of the behavioral effects of anticonvulsant drugs by an external discriminative stimulus in the pigeon.

The effects of the anticonvulsant drugs valproic acid, phenytoin, phenobarbital and diazepam were examined in pigeons performing under a fixed-consecutive-number schedule with and without an added external discriminative stimulus. Under these schedules, a reinforced response run consisted of responding between eight and 12 times on one response key (work key) and then responding once on a second response key (reinforced key). For one group of pigeons, an external discriminative stimulus signaled completion of the response requirement on the work key, whereas no stimulus change was programmed for the other group. Phenobarbital (5-60 mg/kg) and diazepam (0.5-6 mg/kg) produced large decreases in reinforced response runs (accuracy) and rates of responding. The magnitude of these accuracy- and rate-decreasing effects was larger in the group without the external discriminative stimulus. Under both schedules, these drugs produced pronounced increases in the probability of switching to the reinforcement key before completion of the minimal response requirement on the work key. Valproic acid (20-160 mg/kg) and phenytoin (1.25-10 mg/kg) also decreased both accuracy and rates of responding. Although the accuracy-decreasing effects of these drugs were relatively small in magnitude, they were consistently larger in the group without the external discriminative stimulus. These data suggest that the addition of an external discriminative stimulus attenuates the disruptive behavioral effects of anticonvulsant drugs.

Animals↗

PubMed1985

Effects of phenobarbital, clonazepam, valproic acid, ethosuximide, and phenytoin on the delayed matching-to-sample performance of pigeons.

The effects of phenobarbital, clonazepam, valproic acid, ethosuximide, and phenytoin were examined in pigeons performing under a delayed matching-to-sample procedure. Clonazepam, valproic acid, ethosuximide, and phenytoin typically reduced the rate of responding to the sample stimulus, whereas phenobarbital usually increased response rates at high doses. Phenobarbital, clonazepam, and valproic acid produced generally dose-dependent decreases in accuracy; ethosuximide and phenytoin failed to do so. These results suggest that there are qualitative as well as quantitative differences in the effects of anticonvulsant drugs under the delayed matching-to-sample procedure.

Animals↗

PubMed1985

Discriminative stimulus properties of tripelennamine in the pigeon.

Pigeons trained under a two-key drug discrimination procedure eventually learned to discriminate the antihistaminic tripelennamine (5 mg/kg) from saline. When 0.63-7.5 mg/kg doses of tripelennamine were administered in generalization test sessions, the percentage of responses directed to the tripelennamine-appropriate key varied directly with dose. At certain doses, the discriminative stimulus properties of the antihistaminics, diphenhydramine and pyrilamine, clearly generalized to tripelennamine, whereas intermediate generalization was evident with the antihistaminics, chlorpheniramine and promethazine. Chlorpromazine, cimetidine, d-amphetamine, diazepam, morphine, pentazocine, phenobarbital, and sodium valproate failed to produce tripelennamine-like patterns of responding.

Animals↗

PubMed1985

Discriminative stimulus properties of valproic acid in the pigeon.

Pigeons were successfully trained to discriminate 60 mg/kg valproic acid from saline using a two-key drug discrimination procedure. When 5-80 mg/kg doses of valproic acid were administered during generalization tests the percentage of responses directed to the valproic acid-appropriate key varied directly with dose. The effects of administering the training dose of valproic acid at presession injection intervals ranging from 15 to 120 min were described by an inverted U-shaped function; the 30-min interval used during discrimination training engendered the largest percentage of valproic acid-appropriate responses. The discriminative stimulus properties of valproic acid failed to generalize to the anticonvulsant compounds phenobarbital (10, 20 mg/kg), phenytoin (2.5, 5 mg/kg), and ethosuximide (40, 80 mg/kg), indicating that not all anticonvulsant compounds share similar discriminative properties. Clonazepam (0.25, 0.50 mg/kg) and diazepam (1, 2 mg/kg), two benzodiazepines with anticonvulsant properties, produced quite different effects. The stimulus properties of valproic acid generalized to all doses of clonazepam, whereas intermediate generalization was evident with diazepam. Pentylenetetrazol (10, 20 mg/kg), chlorpromazine (5, 10 mg/kg), tripelennamine (2.5, 5.0 mg/kg), d-amphetamine (0.5, 1.0 mg/kg), morphine (1.25, 2.50 mg/kg), and imipramine (2.5, 5.0 mg/kg) induced only saline-like patterns of responding. The concomitant administration of pentylenetetrazol failed to antagonize the discriminative stimulus properties exerted by the training dose of valproic acid.

Animals↗

PubMed1985

Effects of valproic acid and ethosuximide on the responding of pigeons maintained under a multiple fixed-ratio fixed-interval schedule of food delivery.

The effects of valproic acid and ethosuximide were examined in pigeons responding under a multiple Fixed-Ratio 50 Fixed-Interval 90-sec schedule of food delivery. When given acutely 30 min prior to behavioral testing, both valproic acid (40, 60, 80, 100, and 120 mg/kg) and ethosuximide (40, 60, 80, 100, and 120 mg/kg) produced generally dose-dependent decreases in responding under both the Fixed-Ratio and Fixed-Interval components. Detailed analysis of drug effects on the temporal distribution of responding under the Fixed-Interval failed to reveal rate-dependent effects for either drug. Varying the presession injection interval from 15 to 120 min indicated that both valproic acid and ethosuximide reduced responding to the greatest extent when given 30 or 60 min before behavioral testing. These results indicate that the anticonvulsants valproic acid and ethosuximide similarly affect schedule-controlled responding, although previous studies have revealed the drugs to have different effects under other procedures.

Animals↗