P. B. Dews

MODIFICATION BY DRUGS OF PERFORMANCE ON SIMPLE SCHEDULES OF POSITIVE REINFORCEMENT

The basic elements of technique for the use of the free operant are by now quite w e l l k n o ~ n . ~ The purpose of this paper is to illustrate the use of the technique for drug studies by showing how 1 particular procedure has been used to start the analysis of the behavioral effects of some drugs. The work described here has been done on pigeons kept close to a constant weight of lietween EO and

Activity Anorexia: An Interplay Between Basic and Applied Behavior Analysis

0 per cent of the weight a t which they stabilized when fed ad l i b i h m . The pigeons were trained to work as previously described, the arrangement being shown in FIGURE 1. l~ They pecked a t a translucent plastic disk that had variously colored lights behind it. Each peck broke a circuit that enabled it to be recorded and counted. According to a schedule, the pigeon was rewarded (“reinforced”) for pecking with food from a tray that rose so that the food was accessible to the bird for 5 seconds. The distribution of pecks in time, that is, the rate of pecking from time to time, is extremely sensitive to the precise contingencies relating pecks to rewards. For example, if every sixtieth peck is rewarded under the conditions of our experiments, the pigeon comes to peck at high sustained rates. This is a fixed ratio schedule; there is a fixed ratio of reinforcements to pecks. Henceforth this performance will be referred to as “ratio performance.” On the other hand, if a single peck is rewarded when, and only when, a constant interval of time (for example, 15 minutes) has elapsed, there is a period at the beginning of the interval when the bird does not peck a t all, and then there is a fairly smoothly accelerating rate of pecking until the rewarded peck. This is a fixed interval schedule; a fixed interval of time must elapse before a reward can be obtained, and the pattern of pecking engendered by it will be referred to as “interval performance.” It can be arranged that when a light of one color is on, the schedule is fixed ratio, and when a light of a different color is on, the schedule is fixed interval. The bird comes to perform appropriately to each of the schedules according to which light is on. Thus the bird’s performance can be observed on more than 1 schedule during a short period of time without disturbing the animal in any way. This is a “multiple schedule” in the terminology of Ferster and Skinner. They stay adult and in their prime for many years without apparent change. They very rarely show signs of disease and they stand food deprivation for long periods without obvious ill effects. Their food, grain, is very convenient both for use in an automatic magazine and for daily weighing to maintain the birds close to constant weight. Their excellent vision makes use of colored lights as discriminant stimuli possible. These lights are very convenient and make it Departntent of Pharmacology, Harvard Medical School, Boston, Mass.

Interactions of behavioral effects of drugs.

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.

Extrapolation by proximate inference

Interest in the joint effects of two drugs administered simultaneously is as old as scientific pharmacology. Frazer’ systematically explored the joint effects of physostigmine and atropine, and Bernard’ studied the effects of curare and (without knowing it) acetylcholine. The general pharmacological principles for assessment of joint effects are also of some antiquity and are widely accepted among pharmacologists, although there has been bickering, of course, about nomenclature. As good a scheme as any was provided by Gaddum3 over 35 years ago (FIGURE 1 ) . It is presented here as a reminder of a principle not infrequently overlooked by nonpharmacologists: Both dose and effect must be taken into account in determining the nature of the joint action of two drugswhether they are antagonistic or synergistic. If drug A in dose a causes effect of intensity x and drug B in dose b causes the same effect of intensity y , the joint effect of drugs A and B taken simultaneously in doses a and b would not be expected, in general, to be of intensity x + y . The reason that effects are not simply algebraically additive, even for drug pairs whose effects arc strictly additive in Gaddum’s sense, has been emphasized repeatedly: Dose-effect curves are generally not straight lines through the origin. When either a threshold

Reinforcing Stimulus Functions of Drugs: Interpretations

Scientific extrapolation, as in astronomy, is different from legal or regulatory extrapolation, as in arriving at acceptably safe levels of agents. Scientific and technological information is required in the latter process, but scientists fail to contribute when they respond to legal and regulatory questions by attempting purely scientific extrapolation.

THE EFFECT OF MULTIPLE SΔ PERIODS ON RESPONDING ON A FIXED‐INTERVAL SCHEDULE1

The organization of this book, according to ways in which drugs can function as stimulus would have been unthought of 15 years ago. Now behavioral pharmacology is dealing with defined and objectively measurable variables; one can see, at last, an end to the times when pharmacologists, scientists in dealing with other types of drug effects, were content to quote Shakespeare, De Quincey, and Huxley when giving an account of the behavioral effects of drugs.