Search PubMed⌕ Search

Biomedical subjects

D M Thompson

Publications and source records attributed to D M Thompson.

At least 91 records · Page 5Linked to original sources
PubMed1980

Effects of d-amphetamine, cocaine, and phencyclidine on the acquisition of response sequences with and without stimulus fading.

In each of three components of a multiple schedule, monkeys were required to emit a different sequence of four responses in a predetermined order on four levers. Sequence completions produced food on a fixed-ratio schedule. Errors produced a brief timeout. One component of the multiple schedule was a repeated-acquisition task where the four-response sequence changed each session (learning). The second component of the multiple schedule was also a repeated-acquisition task, but acquisition was supported through the use of a stimulus-fading procedure (faded learning). In a third component of the multiple schedule, the sequence of responses remained the same from session to session (performance). At higher doses, d-amphetamine, cocaine, and phencyclidine decreased the overall rate of responding and increased the percent errors in all three components. At lower doses, however, the three drugs produced selective effects on errors. Errors were increased in the learning component at lower doses than those required to disrupt the behavior in the faded-learning component. The performance component tended to be the least sensitive to disruptive drug effects. The data are consistent with the view that stimulus fading can modulate the effects of drugs on acquisition.

Animals↗
PubMed1980

Selective antagonism of the rate-decreasing effect of d-amphetamine by chlorpromazine in a repeated-acquisition task.

Pigeons acquired a different four-response chain each session by responding sequentially on three keys in the presence of four colors. The response chain was maintained by food presentation under a fixed-ratio schedule. When d-amphetamine was administered alone, the overall response rate decreased and the percent errors increased with increasing doses. When a small dose of chlorpromazine, which was ineffective when given alone, was administered in combination with d-amphetamine, the rate-decreasing effect was antagonized. The antagonism was selective, however, in that the error-increasing effect of d-amphetamine was augmented by chlorpromazine. The nature of the joint effect of the two drugs thus depended on the behavioral measure: rate vs. accuracy.

Animals↗
PubMed1979

Effects of methamphetamine and scopolamine on variability of response location.

Methamphetamine and scopolamine were studied in monkeys responding under a multiple fixed-ratio fixed-interval schedule of reinforcement. A response on any one of six levers could satisfy the schedule requirements. Variability of response location was evaluated in terms of switches, where a switch was defined as a response on one lever followed by a response on a different lever. Under baseline conditions the fixed-ratio schedule generated a high rate of responding and a low level of variability, while the fixed-interval schedule generated a low rate of responding and a high level of variability. Both methamphetamine (0.1 to 0.5 mg/kg) and scopolamine (2.4 to 240 microgram/kg) decreased overall response rate and increased variability of response location in each component of the multiple schedule with increasing doses of drug. At lower doses both drugs were found to decrease rate without affecting response variability.

Animals↗
PubMed1979

An experimental analysis of the effects of d-amphetamine and cocaine on the acquisition and performance of response chains in monkeys.

In one component of a multiple schedule of food presentation, monkeys acquired a different four-response chain each session by responding sequentially on three keys in the presence of four geometric forms (learning). In the other component, the four-response chain was the same each session (performance). Both d-amphetamine and cocaine, at the higher doses, disrupted the behavior in the learning component; the overall response rate decreased, the overall accuracy was impaired (i.e., percent errors increased), and there was less within-session error reduction. The performance component was generally less sensitive than the learning component to the disruptive effects of both drugs on rate and accuracy. After pre-feeding or during an extended session, the response rate decreased in both components, but accuracy was generally unaffected. When the four discriminative stimuli in both components were removed, the behavior was disrupted to a greater extent in the performance component. The disruptive effects of both drugs on behavior in the learning component were attenuated when the drugs were administered during the session after the response chain had been acquired. It was concluded that the greater sensitivity of the learning component to disruptive drug effects is related to the relatively weak stimulus control and/or the lower rate of reinforcement associated with that component.

Animals↗
PubMed1978

Neutropenia associated with chrysotherapy for juvenile rheumatoid arthritis.

Severe neutropenia, in the absence of generalized bone marrow depression, is a rare complication in adults receiving chrysotherapy for rheumatoid arthritis and has not been described in children. Isolated, severe neutropenia developed in five children with systemic onset JRA while they were receiving gold injections. This potentially fatal complication occurred within eight weeks of beginning therapy in four patients, and after 24 weeks of well-tolerated therapy in the fifth. Leukopenia preceded neutropenia in two children. Localized infection was successfully treated in one child; septicemia was fatal to a second child. Neutropenia resolved within eight to 14 days of its onset in the four survivors; chelation with dimercaprol in one child did not appear to alter the recovery time. It is suggested that a systemic onset of JRA in children less than 6 years of age identifies a higher risk group developing severe neutropenia during chrysotherapy. Cessation of gold therapy upon recognition of a decreasing neutrophil count may prevent or ameliorate a developing neutropenia; careful observation for, and early treatment of, infection may alter its outcome.

Agranulocytosis↗
PubMed1978

Operant methodology in the study of learning.

A series of experiments is described in which operant methodology is used to study the effects of drugs on "learning." Emphasis is placed on the technique of repeated acquisition as a behavioral baseline for studying this type of transition state. In this technique, each subject is required to learn a new discrimination each session. Multiple-schedule procedures are also described in which acquisition is compared to a "performance" task, where the discrimination is the same each session. The learning baseline is more sensitive to the disruptive effects of a variety of drugs (e.g., cocaine, d-amphetamine, haloperidol) than is the performance baseline. This general finding obtains across procedural variations and species (pigeons and monkeys). The potential usefulness of these procedures for studying both acute and chronic behavioral toxicity is discussed.

Animals↗
PubMed1978

Acute and chronic effects of cocaine on extinction-induced aggression.

Pigeons worked individually in a chamber containing a response key and a mirror. Pecking on the key was controlled by a multiple schedule in which a brief period of continuous food reinforcement alternated with a 5-minute period of extinction. Under baseline conditions, aggressive behavior (responding on the mirror) occurred at the onset of each extinction period. In Experiment I (acute drug administration), the aggressive behavior was decreased by doses of cocaine that had little or no effect on key pecking. Such food-reinforced responding was disrupted, however, by higher doses of cocaine. An attempt to mimic the disruptive drugs effects by a prefeeding manipulation was unsuccessful. In Experiment II (chronic drug administration), some tolerance developed to the disruptive effects of cocaine on the food-reinforced responding, except at the highest dose tested. There was no clear-cut indication of tolerance to the initial effect of cocaine on the aggressive behavior at any dose.

Aggression↗
PubMed1977

Effects of cocaine and fenfluramine on progressive-ratio performance.

Pigeons obtained food on a progressive-ratio schedule that required 8 additional responses for each successive reinforcement. The number of responses in the final completed ratio of the session was defined as the breaking point. When cocaine was administered (IM, 5 min presession), the breaking point increased and then decreased as a function of increasing doses (0.3-10 mg/kg). In contrast, across the same range of doses of fenfluramine, the breaking point only decreased. At doses of each drug that decreased the breaking point, the high running rate of responding was interrupted by pauses. At doses of cocaine that increased the breaking point, the running rate was also disrupted, but the disruption was characterized by lower, irregular rates rather than pausing. The increases in breaking point observed at 3 mg/kg of cocaine were no longer seen when fenfluramine was administered at the same time.

Animals↗
PubMed1977

Development of tolerance to the disruptive effects of cocaine on repeated acquisition and performance of response sequences.

Pigeons obtained food by making four responses on three keys in a specified sequence. Errors produced 5-second timeout periods, during which the keylights were off and responses had no effect. To establish a base line of repeated acquisition, the sequence of correct responses was changed from session to session. Cocaine (3 mg/kg) disrupted the behavior: total errors increased, the relative frequency of perseverative errors increased, the rate of within-session error reduction (learning) decreased and the total trial time (pausing) increased. During repeated drug administration (30-50 sessions), these effects disappeared, i.e., tolerance developed. Tolerance did not develop, however, to cocaine-induced increases or decreases in timeout responding; such effects were nondisruptive in the sense thay they did not reduce the rate of food reinforcement. For comparison, cocaine (3-10 mg/kg) was also studied under a "performance" condition, in which the sequence of correct responses was the same from session to session. Cocaine increased performance errors and produced pausing, but tolerance developed more quickly under the learning condition . The more rapid development of tolerance was presumably due to the stronger stimulus control of behavior under the performance condition.

Animals↗
PubMed1976

Tube leukocyte (monocyte) adherence inhibition assay for the detection of anti-tumour immunity. III. "Blockade" of monocyte reactivity by excess free antigen and immune complexes in advanced cancer patients.

Leukocytes from patients with limited cancer display LAI reactivity whereas leukocytes from patients with metastatic cancer frequently demonstrate no reactivity in the tube LAI assay. The leukocytes (monocytes) of reactive patients react with tumour antigen through specific cytophilic anti-tumour IgG antibody bound to the monocyte's Fc cell surface receptors. The non-reactive monocytes from patients with advanced cancer lacked the ability to bind free cytophilic anti-tumour antibody. Moreover, the serum of the non-reactive patient contained no free cytophilic anti-tumour antibody capable of "arming" normal leukocytes. The serum of patients with large tumour burdens contained free tumour antigenic determinants capable of absorbing free cytophilic anti-tumour antibody from the serum of reactive patients or when preincubated with reactive leukocytes abrogating their LAI responsiveness immunologically specifically. Blocking was immunologically specific; therefore, the specificity must reside in the tumour antigenic determinant since immune complexes are bound nonspecifically. The tumour antigen coat was removed by gentle trypsinization of the monocyte's surface. This restored the monocyte's capacity to react with the sensitizing tumour antigen and to bind free cytophilic antibody from the microenvironment. Nonreactivity in the tube LAI assay of patients with metastatic cancer was not the result of a numerical deficit of circulating monocytes but was mediated by an excess of tumour antigen in the microenvironment of the sensitized monocyte.

Adenocarcinoma↗
PubMed1976

Extinction-induced mirror responding as a baseline for studying drug effects on aggression.

Pigeons worked individually in a chamber containing a response key and a mirror. Responding on the key was controlled by a multiple schedule in which a brief period of continuous food reinforcement alternated with a 5 min period of extinction. Under baseline conditions, aggressive behavior (responding on the mirror) occurred at the onset of each extinction period. After 10 saline control sessions, 5 mg/kg of chlordiazepoxide was injected IM 30 min presession for 60 daily sessions. The drug initially produced a marked decrease in aggressive behavior but had little or no effect on key pecking. The aggressive behavior generally remained suppressed during the chronic drug regimen and returned to control levels when the drug was withdrawn. It was concluded that the technique of extinction-induced mirror responding in pigeons provides a stable, sensitive and recoverable baseline for objectively assessing selective drug effects on aggression.

Aggression↗
PubMed1976

Repeated acquisition of behavioral chains: effects of methylphenidate and imipramine.

A method involving repeated acquistion of behavioral chain was used to assess the effects of methylphenidate and imipramine in individual animals. Pigeons obtained food for completing a 4-response chain, which was changed from session to session. Learning was defined by the decrease in errors across trials within a session; overall accuracy was measured by total errors per session. For comparison, the drug tests were also conducted under a performance condition, in which the 4-response chain was the same from session to session. In general, both drugs increased total errors per session as a function of dose under both the learning and performance conditions. The error-increasing effect was greater with imipramine than with methylphenidate and was detected at lower doses under the learning condition than under the performance condition. Under the learning condition, the higher doses of both drugs decreased the rate of within-session error reduction. Although neither drug enhanced accuracy at any of the doses tested, the lower doses of methylphenidate slightly decreased total trial time under both the learning and performance conditions.

Animals↗