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Biomedical subjects

G R Wenger

Publications and source records attributed to G R Wenger.

9 recordsLinked to original sources

Effects of drugs of abuse on acquisition of behavioral chains in squirrel monkeys.

The acute effects of various drugs of abuse on the acquisition of chains of behavior were assessed in squirrel monkeys trained to respond on three keys for food. Each new session the monkeys acquired a different four-response chain by responding sequentially on three keys in the presence of four different stimuli. Incorrect responses inactivated the keys and darkened the chamber for 10 s (time-out). Dose-effect curves were obtained by administering the drugs intramuscularly before the session and recording their effects on the rate and accuracy of responding. Cocaine, d-amphetamine, and delta 9-tetrahydrocannabinol all decreased the accuracy and rate of responding within the dose range of 0.56-3 mg/kg. The highest dose of morphine tested (3 mg/kg) produced parallel decreases in the accuracy and rate of responding in some monkeys but had no effect at lower doses. These drugs decreased within-session accuracy though clearly acquisition did occur, but high doses of caffeine (30 and 56 mg/kg) prevented acquisition and recovery of performance and, furthermore, at 30 mg/kg these effects were observed in the absence of decreases in the rate of responding. The drugs of abuse tested all produced dose-related decreases in both the accuracy and rate of responding, and the decreases in accuracy were primarily observed only at doses that also decreased response rates. Therefore, based on these results from nonhuman primates each of these drugs has the potential to alter learning particularly when doses that disrupt other behaviors are administered.

Animals

Titrating matching-to-sample performance: effects of drugs of abuse and intertrial interval.

Previous reports have shown that increasing the length of the intertrial interval (ITI) in a matching-to-sample schedule of reinforcement results in increased matching accuracy. This has traditionally been interpreted in the context of proactive inhibition, the disruption of memory for a stimulus as a consequence of events that occurred prior to the presentation of the stimulus. In an effort to more fully characterize a titrating matching-to-sample baseline, the effect of ITI ranging from 0-30 s was determined in pigeons trained to respond under the titrating matching-to-sample procedure. In addition, the effect of ITI length on the dose-response curve for pentobarbital, phencyclidine, D-amphetamine, and cocaine were determined. Surprisingly, performance under the titrating matching-to-sample was not altered as a function of ITI length, nor did the effects of the four drugs of abuse change as a function of ITI length. These results suggest that performance under the titrating matching-to-sample is under a different control than matching-to-sample using fixed delays.

Amphetamine

The effects of cocaine in combination with other drugs of abuse on schedule-controlled behavior in the pigeon.

The present experiment sought to provide information regarding the consequences of combining cocaine with other drugs of abuse. The effects of cocaine alone and in combination with d-amphetamine, caffeine, morphine or delta-9-tetrahydrocannabinol were determined in five male white Carneaux pigeons responding under a multiple fixed-ratio 30, fixed-interval 600 schedule (mult FR FI). Drug interactions were studied by redetermining the cocaine dose-response curve in the presence of various fixed doses of the other drugs. Under the mult FR FI schedule, when cocaine (1 to 10 mg/kg) was combined with inactive doses of d-amphetamine (0.1, 0.3, 1.0, and 1.8 mg/kg), caffeine (10, 30, and 100 mg/kg), morphine (0.3, and 1.0 mg/kg), and delta-9-tetrahydrocannabinol (0.1 mg/kg), the FR and FI response rate dose-response curves were not shifted relative to the cocaine-alone curves. When cocaine was combined with an active dose of a drug which decreased response rate when given alone (0.3 mg/kg delta-9-tetrahydrocannabinol and 3 mg/kg morphine), the position of the response rate dose-response curves shifted compared to the cocaine-alone curves. The most frequent and consistent outcome of these interactions can be described as less than or approximately equal to an effect-additive interaction. Thus, these data indicate that the potential consequences of coabusing cocaine with the drugs tested in the present experiment can most often be predicted from the effects of each drug when taken alone.

Animals

Effects of clozapine, chlorpromazine and haloperidol on schedule-controlled behavior.

The effects of clozapine, chlorpromazine, and haloperidol were determined in mice and pigeons responding under a multiple fixed-ratio 30, fixed-interval 600 sec schedule of food presentation. In both species, low doses were without effect and moderate to high doses of all three antipsychotics decreased responding. In contrast to other behavioral tests used to predict antipsychotic activity, clozapine was equipotent or more potent than chlorpromazine in decreasing responding under the multiple fixed-ratio 30, fixed-interval 600 sec schedule. The order of potency observed in the mouse was: haloperidol greater than chlorpromazine greater than or equal to clozapine. The order of potency in the pigeon was: haloperidol greater than clozapine greater than chlorpromazine. In mice and pigeons, the rate of responding under the fixed-ratio component was decreased at lower than, or the same doses of clozapine as that required to decrease fixed-interval responding. However, in both species, chlorpromazine and haloperidol decreased fixed-interval responding at lower doses or the same dose as that required to decrease fixed-ratio responding.

Animals

Testing for behavioral effects of agents.

In the present state of science no morphological or chemical changes may be detectable at a time when behavior is profoundly disturbed, as in schizophrenia. Until we are reassured to the contrary, we must assume that exogenetic intoxication can produce changes detectable only as behavioral changes. Therefore behavioral toxicology must be studied. In contrast to toxic manifestations such as lethality or carcinogenicity, which tend to be unequivocal and irreversible, behavioral changes are like physiological changes in that they are quantitative, changing in time, and relate to variables with a considerable range of normal variability. An experiment on behavioral teratology in mice is described and the results used to illustrate the limits of the possible in behavioral toxicology. From reported and observed variability it is surmised that changes that occur in as many as 1 per 100 of the population or average as large as a 10% decrement will still be too small to be detected by direct experiment. Such risks are frequently unacceptable. Reasons are given for hoping that epidemiological studies may be able to supplement experimental toxicological studies to provide a better assessment of risk of small impairments or rare susceptibility.

Animals

The effect of phencyclidine and ketamine on schedule-controlled behavior in the pigeon.

Pigeons were trained under a multiple schedule of food presentation with alternating 30-response fixed-ratio (FR-30) and 10-minute fixed-interval (FI-10) components. Average rates of responding were 2.9 and 0.55 responses/sec, respectively. Both phencyclidine (0.03-3.0 mg/kg i.m.) and ketamine (0.1-30.0 mg/kg i.m.) increased response rates at low doses while decreasing response rates at high doses during the FI-10 component. Only a dose-related decrease in response rates was seen in the FR-30 component with both phencyclidine and ketamine. In individual birds, the maximum rate increases in the FI-10 component ranged from 110% to 163% of the control rate. The rate increases in the FI-10 component depended on the control rate of responding. The effects of phencyclidine and ketamine were qualitatively similar to d-amphetamine (0.1-10 mg/kg i.m.).

Animals

The effects of phencyclidine, ketamine, delta-amphetamine and pentobarbital on schedule-controlled behavior in the mouse.

The response of mice of breaking a light beam onto a photocell was programmed to produce food according to a multiple schedule with alternating 30-response fixed ratio, 300-second fixed interval (FR-30 FI-300 sec) components. Training was standardized for all mice, and stable patterns of responding that were similar to those described for other species and responses under this schedule developed quickly. The effects of pentobaribtal, delta-amphetamine, phencyclidine and ketamine were studied. At some dose, each of the four drugs produced an increase in rate of responding; the increase was proportionately greater at low rates of responding than at higher rates. At some dose range, delta-amphetamine, ketamine and phencyclidine produced dose-related increases in FI average rates were to 1.83, 1.25 and 1.32 times the control rate for delta-amphetamine (1 mg/kg), ketamine (100 mg/kg) and phencyclidine (3 mg/kg), respectively. Phencyclidine and ketamine thus showed some "amphetamine-like" effects in the mouse. Pentobarbital increased (1.25 times the control rate) both the FR and FI response rates at a dose of 3 mg/kg. Higher doses of pentobarbital progressively decreased both FR and FI response rates in a parallel fashion.

Animals