W. H. Morse

Second-Order Schedules of Drug Injection

Key-press responding of squirrel monkeys produced intravenous injections of cocaine under two simple types of schedule. Under a fixed ratio schedule, every 30th response produced an injection; steady responding at high rates of over one per second were maintained during each fixed-ratio component. Under a fixed-interval schedule, the first response occurring after a fixed time of 5 min produced an injection; there was a pause at the start of each interval and then progressively increasing responding until cocaine was injected at the end of the interval. Both squirrel monkeys and rhesus monkeys also were studied under second-order schedules of drug injection. Under one type of second-order schedule, studies only in squirrel monkeys, completion of each fixed-interval component produced only a 2 sec light; completion of the 10th fixed-interval component produced the brief light and an intravenous injection of cocaine. Under a second type of second-order schedule, each fixed-ratio component completed during a fixed time interval (5 or 60 min) produced only a 2-sec light; the first fixed-ratio component completed after the interval of time elapsed produced the brief light and an intravenous (squirrel monkeys) or intramuscular (rhesus monkeys) injection of cocaine. Under both types of second-order schedules, repeated sequences of responding were maintained during each session and characteristic fixed-interval or fixed-ratio patterns of responding were controlled by the brief visual stimuli.

Effect of Amobarbital and Chlorpromazine on Punished Behavior in the Pigeon

SummaryThe effects of amobarbital and chlorpromazine were studied on punished behavior in the pigeon. Key-pecking responses, maintained by a variable-interval schedule of food reinforcement, were punished by brief electric shocks. Under this simultaneous food and punishment schedule, responding is suppressed and occurs at a fairly uniform rate that is inversely related to the punishment intensity. Amobarbital partially restores responding suppressed by punishment, but chlorpromazine has no tendency to attenuate suppression by punishment.

Activity Anorexia: An Interplay Between Basic and Applied Behavior Analysis

The relationship between basic research with nonhumans and applied behavior analysis is illustrated by our work on activity anorexia. When rats are fed one meal a day and allowed to run on an activity wheel, they run excessively, stop eating, and die of starvation. Convergent evidence, from several different research areas, indicates that the behavior of these animals and humans who self-starve is functionally similar. A biobehavioral theory of activity anorexia is presented that details the cultural contingencies, behavioral processes, and physiology of anorexia. Diagnostic criteria and a three-stage treatment program for activity-based anorexia are outlined. The animal model permits basic research on anorexia that for practical and ethical reasons cannot be conducted with humans. Thus, basic research can have applied importance.

EFFECTS OF DRUGS ON CHARACTERISTICS OF BEHAVIOR MAINTAINED BY COMPLEX SCHEDULES OF INTERMITTENT POSITIVE REINFORCEMENT

Behavioral base lines with several reproducible properties are useful in investigating the effects of drugs on learned behavior. Differential drug effects on interrelated characteristics of behavior make possible detailed analyses of drug action. In addition, behavioral base lines with complex properties offer an advantage in that they are more sensitive to the effects of drugs than are simple base lines. A simple base-line performance is generated by a fixed-ratio schedule in which an animal is reinforced each time a small, constant number of responses is emitted. Following reinforcement, the animal responds a t a high, fairly constant rate until the next reinforcement. I t has been frequently noted that performance under this schedule is refractory to drugs. The insensitivity of behavior maintained by small ratio schedules is reflected both in the need for using relatively large quantities of a drug in order to observe any change in behavior, and in the precipitousness with which the change occurs. Once the dose is made large enough to affect the animals performance, a gross disturbance in motor coordination also takes place. When used in a base line that contains other schedules of reinforcement, however, a fixed-ratio schedule becomes a valuable tool, that is, where the fixed-ratio performance may be viewed as a characteristic component of a more complex behavior. FIGURE 1 shows the insensitivity of small ratio schedules and the specificity of drug action upon the multiple characteristics of a complex behavior. This curve is a cumulative record of pecking responses for a single pigeon on a day when it received a 4 mg. dosage of sodium pentobarbital. The number of responses is on the ordinate, and time is on the abscissa. This pigeon was maintained a t 80 per cent of normal body weight on a regimen of partial food deprivation. The short diagonal marks indicate the points a t which the response was reinforced with food. The behavioral base line was a multiple schedule containing 2 component schedules of reinforcement. In the presence of 1 stimulus, the pigeon was reinforced on a small fixed-ratio schedule-the 50th response emitted after the onset of the stimulus was reinforced. In the presence of the other stimulus the schedule was a fixed interval-the first response emitted after 10 minutes from the onset of the stimulus was reinforced. The early portion of the record shows a typical performance. When the ratio component was present, the animal responded a t a high constant rate. When the interval component was present there was a positively accelerated curve up to the reinforcement. Later portions of the figure make

Behavioral effects of chronically administered cocaine in squirrel monkeys

Cocaine (0.1 or 0.3 mg/kg/h) was infused continuously from osmotic minipumps during 14-day periods in three squirrel monkeys trained under a fixed-interval schedule of stimulus-shock termination. Chronic exposure to 0.1 mg/kg/h cocaine increased response rates during control sessions for two subjects, and rates returned to pre-infusion levels after the osmotic minipumps were removed. During chronic administration with 0.3 mg/kg/h cocaine, tolerance developed to the gross behavioral effects observed initially in all subjects and to the rate-suppressing effects observed in one subject. Using a cumulative-dosing procedure, cocaine was administered IV acutely once per week before, during and after each chronic administration with cocaine. The acute effects of cocaine on schedule-controlled responding before chronic administration and during chronic exposure to 0.1 and 0.3 mg/kg/h cocaine were similar, providing no evidence of sensitization or tolerance.

Effects of Drugs on Schedule-Controlled Behavior and Cardiovascular Function in the Squirrel Monkey

Environmental circumstances can modulate physiological functions and alter the action of drugs. There is now much systematic information on how the behavioral effects of drugs are modified by environmental determinants of behavior. Most drugs have selective actions on behavior in different situations, and predictions about the behavioral effects of a drug require knowledge about the conditions under which the drug is acting and the determinants of behavior in that situation. In some instances the profound effects of environmental factors in modifying the actions of drugs apply to the toxic effects of drugs; for example, it is now well known that changing the environmental circumstances can markedly enhance the lethality of amphetamine (Chance, 1946, 1967; Gunn and Gurd, 1940; Hohn and Lasagna, 1960; Weiss et al., 1961.)

Contributions of peter B. Dews (1922‐2012) to the experimental analysis of behavior

Peter Dews died on November 2, 2012 after several years of declining health. He is widely recognized as the single individual most responsible for the emergence of behavioral pharmacology as an experimental science concerned with the rigorous assessment of the behavioral effects of drugs. Understandably, his preeminence in behavioral pharmacology has overshadowed recognition, or even awareness, of his commitment and experimental contributions to the study of behavior. Yet his commitment to the study of behavior is easily documented. He was on the original editorial board of the Journal of the Experimental Analysis of Behavior (the only nonpsychologist), and served as a reviewer for the journal for 15 years. Of the research he conducted alone, there are more papers devoted to the analysis of behavior than to experiments with drugs. From the early 1960s, virtually all his independent research was on the quantitative study of schedule-controlled performances. In an interview with John Harvey (Harvey, 2011), Dews said that the most significant influences on his career were Skinner’s early work and Ferster and Skinner’s (1957) research showing that scheduling procedures could control long sequences of complex behavior. Dews’s interest in ways to study the behavioral effects of drugs developed from his earlier experiences in England conducting research on an extract of marijuana and on the antihistamine pyrilamine. He had sought advice from other English pharmacologists on ways to study behavior in experimental animals, but nothing that was suggested (Pavlovian conditioning, maze-learning) seemed suitable to Dews for determining quantitative dose functions in real time. There are several accounts of the earlier career of Dews and his meeting with Fred Skinner and Charlie Ferster in January 1953 (Dews, 1997; Morse, 2005, Morse, 2013). When they first met, Dews had never heard of B. F. Skinner and he didn’t know what Ferster and Skinner were studying, but he instantly recognized the paper tracings of cumulative responses as the equivalent of slope kymograph physiological recordings. He realized that the procedures producing these tracings could be what he had been looking for: a way to measure the effects of graded doses of a drug on a quantitative aspect of behavior in continuous time. Ferster understood that Dews appreciated what he was seeing even without specific knowledge of what the experiments were about, and he invited Dews to come back and make injections in the middle of sessions to see what would happen. Ferster thought it was wonderful to have Dews coming over and altering schedule performances with injections of pentobarbital, antihistamines, LSD, and the marijuana derivative synhexyl, but this wasn’t really Dews’s style. Ferster helped Dews begin systematic experiments in the Department of Pharmacology at Harvard Medical School to study the effects of drugs on schedule performances in the pigeon. In his initial experiment, Dews followed Ferster’s advice and studied pecking in pigeons where a brief presentation of food followed a peck under two different scheduling conditions. The drug he chose to study was pentobarbital, and its effects on the rate and pattern of pecking was dose-dependently different under the two schedule conditions (Dews, 1955a). This first experiment influenced Dews profoundly. He realized that he had, at last, quantitative procedures for studying the effects of drugs on behavior in a pharmacologically rigorous way. Equally important, he appreciated the positive advantages of Skinner’s general approach of studying isolated behavior in a controlled space free of extraneous influences, and describing it in objective physical terms. In subsequent experiments he I am indebted to James McKearney and Patricia Morse for helpful comments on earlier drafts of this manuscript and to Jonathan Katz for both his comments and for his help in preparing the finished manuscript. Address correspondence to: pmorse@centurytel.net doi: 10.1002/jeab.253 JOURNAL OF THE EXPERIMENTAL ANALYSIS OF BEHAVIOR 2017, n/a–n/a

Pharmacological studies of behavioral influences on cardiovascular function

Squirrel monkeys, prepared with chronic arterial and venous catheters, responded (pressed a key) under fixed-ratio schedules of termination of a stimulus associated with electric shock or under fixed-ratio schedules of food presentation. Although there was no necessary correlation between schedule-controlled responding and cardiovascular changes, pronounced elevations in both heart rate and blood pressure occurred during and just after brief periods of fixed-ratio responding. These episodic increases in blood pressure and heart rate were as marked under schedules of food presentation as under schedules of stimulus-shock termination. Thus, these episodic changes appear to be more dependent upon the schedule-controlled behavior than upon the type of event maintaining the behavior. Pharmacological studies indicated that under the conditions of the behavioral experiments the squirrel monkey has a relatively high degree of cardiac sympathetic tone; however, blood pressure elevations produced by administration of 1-norepinephrine were associated with an increased parasympathetic tone and decreased heart rate. The reflex bradycardia induced by 1-norepinephrine was inhibited during periods of schedule-controlled responding, suggesting that environmental and behavioral factors can not only modulate the parameters of physiological variables but also modulate this basic cardiovascular control system.