Differential Drug Effects as a Function of the Controlling Consequences


One of the central themes during the initial period in the development of behavioral pharmacology was the issue of whether motivational factors influence the effects drugs have on behavior. Though seemingly a straightforward question, the translation of this problem into an experimentally addressable form was, and continues to be, somewhat difficult. Motivational concepts almost inevitably pose formidable experimental problems, and studies designed to resolve those problems have often yielded equivocal results. Typically, however, the question has been approached experimentally by comparing the effects of various drugs on behavior controlled by different types of events, e.g., food presentation and escape from electric shock. Presumably, different events and the behavioral consequences associated with them engendered different motivational states. The influence of motivational factors as determinants of drug action should then be reflected by differential changes in overt behavior when the organism is given certain drugs.

This approach had one rather substantial problem that was not always recognized. Behavioral consequences are important in several different ways, not only when they differ on some hedonic dimension, but also depending precisely on how they are arranged or scheduled with regard to behavior. Characteristics of behavior such as the rate, duration, intensity, and temporal distribution of responding are typically quite distinctive under different schedules even when only a single consequence is arranged. Further, it has been shown repeatedly that one of these characteristics, the rate and pattern of responding, can contribute significantly to the effects many drugs have on behavior (). It remains possible that other less intensively studied factors, quite apart from the type of consequence, also play an important role in determining the behavioral effects of drugs.

Because it has been shown that the effects of various drugs on behaviors maintained by only one type of event can depend at least on the schedule-controlled rate and pattern of responding, experimental efforts directed towards understanding whether the nature of the event maintaining responding affects drug action cannot be conducted arbitrarily (). For example, if one is interested in comparing drug effects on behaviors maintained by food and shock, it would be less meaningful to compare performances under a continuous shock-postponement (avoidance) schedule with those under a fixed-interval food-presentation schedule than it would be to compare drug effects under comparable fixed-interval schedules of food or termination of a stimulus correlated with shock. In the first comparison, even if overall rates of responding were similar, it is almost certain that the temporal distribution or the patterning of responding would be quite different. Consequently, most individuals that have recently examined drug effects on behaviors maintained by different events have consistently emphasized the importance of making such comparisons under conditions as comparable as possible ().

Figure Comparable performances of squirrel monkeys responding under S-minute fixed-interval schedules with different maintaining events. The pens react to baseline at reinforcement. Each component was separated by a one-minute timeout period during which all illumination in the chamber was extinguished. Food presentation consisted of the delivery of a 300 mg Noyes banana-fLavored pellet; shock presentation was a 200 msec 9 mA electric shock delivered to the shaved portion of the monkey’s tail which was held motionless by a small stock. Under the stimulus-shock termination schedule, 9 mA shocks were scheduled to occur beginning one second after the elapse of the S-minute fixed interval; a response after the 5-minute interval had elapsed terminated the prevailing stimuli and shock schedule and produced the timeout period. Cocaine hydrochloride was injected via an indwelling intravenous catheter connected to a motor-driven syringe; a response after the S-minute fixed interval produced a 50 ug/kg infusion of cocaine. Note that performances maintained by the different events are quite similar despite their various characteristics and means of administration shows similarities in performances maintained by different events under comparable schedules of reinforcement. These records depict responding of squirrel monkeys maintained under 5-minute fixed-interval schedules of food presentation, shock presentation, stimulus-shock termination, or intravenous cocaine self-administration. Despite the marked differences in the nature of these consequent events, the schedule-controlled rate and pattern of responding maintained by each was remarkably similar. Comparisons of drug effects under conditions such as these minimize the influence of other variables and permit reasonably straightforward analyses.

This approach was taken in experiments by Kelleher and Morse () and by Cook and Catania (). These investigators studied the effects of several different drugs (e.g., chlorpromazine, d-amphetamine, chlordiazepoxide, and imipramine) on behavior maintained under similar schedules of food presentation, escape from continuous electric shock, or termination of a stimulus associated with electric shock. Although Cook and Catania () studied only fixed-interval schedules, Kelleher and Morse () compared drug effects under both fixed-interval and fixed-ratio schedules of either food presentation or stimulus-shock termination. None of the drugs in these experiments had behavioral effects that depended on the type of event maintaining behavior. However, in the Kelleher and Morse () study, the effects of d-amphetamine and chlorpromazine were related to whether responding was maintained under the fixed-interval or fixed-ratio schedules. These findings were of considerable significance because they suggested that the nature of the event controlling behavior was less important than the schedule under which that event occurred. Motivational factors, at least as assessed in this manner, appeared superfluous in attempting to account for the behavioral effects of drugs.

Until recently, there have been very few additional experiments that focused on comparisons of the effects of drugs on behaviors maintained by different events. Tremendous progress has occurred recently because of the development and refinement of certain procedures that have permitted an examination of more diverse events under conditions where the behavioral performances are often nearly identical. Experimental efforts addressing the question of differential drug effects as a function of the controlling consequences have incorporated many of the fundamental principles in behavioral pharmacology. The results of these studies, therefore, have general implications for principles in this field. In addition, these experiments have also helped clarify and delineate other important environmental determinants of the behavioral effects of drugs. Continued research, therefore, should yield valuable information for developing a broad perspective and better understanding of drugs of abuse.


Behavior maintained by different events

Recent studies comparing drug effects on behavioral performances controlled by different events have incorporated a number of developments in the experimental analysis of behavior maintained under various schedules of reinforcement. These advances have extended the range of useful consequent events and the specific conditions under which they can be studied.

Several experiments, to be described below, compared the effects of various drugs on responding maintained either by the presentation of food or electric shock. Figure 1 showed that performances maintained by response-produced shock were indistinguishable from those maintained under similar schedules by food, i.v. cocaine administration, or by the termination of a stimulus in the presence of which shock occurred. Although a great deal has already been written about the maintenance of behavior by shock presentation (), a few brief summary points are necessary for much of the material that is to follow in this chapter.

Noxious events, such as shock, have typically been used either as punishing stimuli that, when presented, suppress responding or as stimuli that maintain responding by their termination or postponement. However, several studies now indicate that response-produced shock presentation can also maintain responding and that both reinforcing and punishing effects of shock presentation can be obtained in the same organism at the same time (). Recent experiments have also demonstrated that behavior can be maintained simultaneously under concurrent schedules when one schedule programs response-produced shock and the second consists either of stimulus-shock termination () or shock avoidance (). In these studies responses on one lever produced shock; at the same time, responses on a second device, either a lever or chain, were maintained by the postponement of shock or by the termination of the stimulus-shock schedule. Thus, animals were responding to produce a shock that, at the same time, they were also responding to terminate or postpone. Performances maintained under each concurrent schedule were comparable to those obtained when these schedules have been arranged individually.

Taken together, these several findings indicate that the reinforcing or punishing properties of behavioral consequences are not invariant features of an event, but depend on other factors such as the schedule under which that event is presented and the history of the organism. Significantly, these factors not only determine the effects that consequent events have on behavior, but also appear to influence the effects of a variety of drugs. For example, the effects of amphetamine are different depending on whether responding is suppressed or maintained by shock delivery. Punished behavior is typically decreased by amphetamine, whereas behavior maintained by shock is increased (). These results reaffirm the view that the schedule can be a critical aspect in determining the effects both of events and of drugs on behavior.

The finding that animals respond to produce shock by no means implies that the physical properties of the shock have changed. The same intensity of shock that increases responding under one condition will continue to suppress performance of the same animal under another condition. It is also apparent that this is not a feat obtained only by means of experimental deceit and that the organisms in these studies are insensitive to the prevailing contingencies. Performances simultaneously maintained under concurrent schedules of shock avoidance and fixed-interval shock presentation, for example, are characteristic of those maintained when these behaviors are studied in isolation, thereby indicating precise differential control by the two schedules in effect.

Dual behavioral effects have been found with stimuli other than shock (), indicating that a variety of other consequent events do not have static, immutable behavioral effects. Stimuli have multiple effects on behavior. More extensive investigation of the generality of these effects and an exploration of their implications will undoubtedly provide a more meaningful understanding of processes controlling behavior. Eventually, such efforts may help in clarifying some of the problems involved in apparently anomalous habitual behaviors such as substance abuse.

Drug effects on behavior maintained by food, electric-shock presentation and stimulus-shock termination

Summary and conclusions

This chapter has reviewed much of the recent experimental information pertaining to our current understanding of the role of the consequent event as a determinant of the behavioral effects of drugs. Although it appeared at one time that the nature of the consequences controlling behavior were less important than other factors, such as the schedule-controlled rate and pattern of responding, this conclusion no longer seems true. Several experiments described in the preceding sections provide overwhelming evidence that the type of event controlling behavior can be an important aspect of the environment contributing to the behavioral effects of a number of drugs.

Despite the fact that the event can be an important factor, other features of the behavioral situation such as the schedule under which the event is presented can also play a role. This was clearly seen with d-amphetamine which increased responding maintained by food or stimulus-shock termination under fixed-interval schedules; when these same events controlled responding under fixed-ratio schedules, however, d-amphetamine decreased food-maintained responding but increased responding maintained under the termination schedule. Differential effects were also obtained with chlordiazepoxide under fixed-interval but not fixed-ratio schedules. These findings point to the increasing level of complexity involved in behavioral pharmacology as progress is made in attempting to characterize determinants of the behavioral effects of drugs.

It has been clear for some time that environmental factors can play an exceedingly influential role in determining the effects of a wide variety of abused drugs. Environmental factors also exert tremendous control over behavior and unquestionably influence its distinctive nature. Many of the factors that are responsible for the subtle idiosyncratic characteristics of behavior, as well as its more global features, can be traced directly to the interaction of behavior with the environment. Ongoing and newly emerging behavior has inevitable consequences which not only affect that behavior directly and immediately, but also that of future behavior as well.

Drugs of abuse also produce extremely powerful effects on behavior. It is significant that many of the variables that control behavior also determine the behavioral effects of drugs. This natural reciprocity between the study of behavior and the behavioral effects of abused drugs is beneficial because research on drug abuse advances knowledge in both fields. Despite the fact that the effects of drugs on ongoing behavior represent a vast integration of changes occurring at several different levels, many of the principal determinants of the behavioral effects of abused drugs can be attributed directly to specific aspects of the environmental conditions under which that behavior has occurred or is occurring. It has been shown repeatedly that the same drug can have completely opposite effects on behavior depending on any of several influential environmental variables.

An emphasis on the clarification and significance of environmental variables, such as the role of the maintaining event, in attempting to understand the behavioral effects of abused drugs is not meant to deny or negate the importance of other factors. Changes in behavior produced by drugs, however, are often most conspicuous because of the excessive nature, intensity, and disruption that typically occurs. Drugs of abuse produce a variety of pharmacological effects that are usually physiologically consistent. Yet, at the level of behavior, there are often noteworthy discrepancies, particularly in what seems to be a drug’s abuse potential. Many abused drugs, for example, produce marked uniform effects on psychomotor activity, physiological and sensory processes that are reasonably consistent from individual to individual. However, many of these drugs are not ubiquitously abused nor do they produce entirely uniform behavioral effects. This suggests that perhaps many of the changes in behavior produced by drugs of abuse, as well as a drug’s abuse liability, may be related more directly to environmental than to pharmacological variables. Future research will hopefully identify and provide a balanced account of the importance and generality of both environmental and pharmacological determinants of the behavioral effects of abused drugs.

Selections from the book: “Behavioral Pharmacology of Human Drug Dependence”. Travis Thompson, Ph.D., and Chris E. Johanson, Ph.D., eds. Presents a growing body of data, systematically derived, on the behavioral mechanisms involved in use and abuse of drugs. National Institute on Drug Abuse Research Monograph 37, July 1981.