An Addiction Science Network Resource

Reprinted from J.L Katz and S.R. Goldberg (1987), Second-order scedules of drug injecion. In M.A. Bozarth (Ed.), Methods of assessing the reinforcing properties of abused drugs (pp. 105-115). New York: Springer-Verlag.
 
Brain Reward System
Back to book TOC
(Search book contents) (Search entire ASNet)


Chapter 5

Second-Order Schedules of Drug Reinforcement
 

Jonathan L. Katz and Steven R. Goldberg

NIDA Addiction Research Center
P.O. Box 5180
Baltimore, MD 21224
and
Department of Pharmacology and Experimental Therapeutics
University of Maryland School of Medicine
Baltimore, MD 21201
 
 

Introduction

One of the most noteworthy features of the behavior of human drug abusers is the extent to which their behavioral repertoire consists of responses maintained by procurement, preparation, and the ultimate administration of drug. Since abusers can be totally consumed with drug-seeking and drug-oriented behaviors and since drug abuse is obviously maladaptive, many theories of drug addiction and abuse have emphasized what were thought to be fundamental pathologies in personality or motivations unique to the drug abuser. However, as Sidman (1960) noted many years ago, pathological states in behavior, as in medicine, can be manifestations of normal processes which are determined, lawful extensions of normal functioning in what is often an atypical environment. Excessive behavior maintained by drug, therefore, may be functionally no different from other behavior but maintained in an environment that promotes its predominance. Following the above interpretation, laboratory studies can examine the extent to which drug-seeking or drug-taking behavior is different from behavior maintained by other stimulus events. A related question is whether the reinforcing effects of drugs are fundamentally different from the reinforcing effects of other events that maintain behavior.

Initial laboratory studies of drugs as reinforcing events were primarily concerned with determining whether drug injections could maintain behavior in experimental animals. With few exceptions, early studies did well if reinforcement by drug injection was firmly established. The meager amounts of behavior maintained by drugs in those studies distinguished drug-maintained behavior from behavior maintained by more conventionally used reinforcing events, such as food or water presentation, since these latter behaviors were typically maintained at higher rates and with patterns characteristic of the schedule under which the reinforcer was presented. Ironically, the distinguishing features of drug-maintained behavior in laboratory studies were in contradistinction to the excessive features that distinguish human drug-seeking and drug-taking.

An experiment by Pickens and Thompson (1968) on cocaine-reinforced behavior in rats indicated that differences in the manner of scheduling intravenous cocaine injections and more conventional reinforcers accounted for some of the differences between the levels of behavior maintained. Since venous catheters remained patent for relatively short times, drug-maintained responding could be studied only during relatively few experimental sessions. In order to collect more data, those sessions were longer than those used for studying behavior maintained by other events. Performances maintained by cocaine injection were characterized by long pauses and rates of responding that were inversely related to dose of cocaine. In contrast, under schedules of food presentation during shorter experimental sessions, pauses after reinforcement were relatively short and rates of responding were directly related to the amount of food presented. When food-maintained responding was studied in long experimental sessions, however, the rates of responding were, as with cocaine injection, inversely related to the magnitude of reinforcement. Thus, food-maintained behaviors could be made more similar to cocaine-maintained behaviors if conditions of the study were modified to resemble those under which drug-maintained behavior was studied.

Other investigators have modified conditions under which drug-maintained responding was studied so that performances maintained by drug were more similar to those typically maintained by reinforcers such as food presentation. The implications of progress along this line were discussed by Morse (1975). With technical innovations for prolonged catheter life and, importantly, the discovery of procedures and combinations of parameter values that yielded optimal performances, responding maintained by drug injections has recently more closely approximated that maintained by more conventional reinforcing events.

Events that function as reinforcers generally have effects on behavior in addition to reinforcing effects. In most studies responding is maintained by reinforcers presented repeatedly throughout an experimental session according to some schedule. Under these conditions effects of the stimuli other than reinforcing effects can interfere with subsequent responding. Large magnitudes of food as a reinforcer can have satiating effects that interfere with subsequent responding (Goldberg, 1973; Sidman & Stebbins, 1954). Electric-shock presentation can elicit responses that are incompatible with the reinforced response (Smith, Gustavson, & Gregor, 1972). Drugs can have direct pharmacological effects on rates of responding (e.g., Kelleher & Morse, 1968) in addition to their reinforcing effects. For example, Pickens and Thompson (1968) found that within-session intravenous injections of cocaine in rats trained under fixed-ratio schedules of food presentation produced pauses in responding that were similar to those observed after injection in rats self-administering cocaine. Thus, the pauses following cocaine reinforcement were likely due to a direct effect of the drug on subsequent responding.

The conditions under which drugs maintain performances similar to those maintained by other reinforcers often are those that minimize direct pharmacological effects that can interfere with subsequent behavior. One method for minimizing direct pharmacological effects on subsequent responding is to schedule a time-out period following each injection during which stimuli are absent and responses of the subject have no scheduled consequences. Scheduling time-out periods following injections often produces patterns and rates of responding maintained by drug injection that more closely approximate those maintained by other reinforcers (Goldberg, 1973; Kelleher, 1975; Woods & Schuster, 1971).

One function of the time-out following drug injection is that it spaces response-produced injections such that cumulative direct effects of the drugs are lessened. Some schedules have similar effects. Under fixed-interval schedules, for example, there is a minimum time period between successive injections. Although long interval schedules are more effective in minimizing cumulative drug effects, responding may become poorly maintained as the interval is extended. Second-order schedules have been used to maintain extended sequences of responding between scheduled injections. Under one type of second-order schedule, each nth response produces a brief visual stimulus (fixed ratio or FR schedule), and the first FR completed after the lapse of a fixed interval (FI) produces the stimulus accompanied by a drug injection. The entire schedule can be designated FI (FR:S) following the nomenclature of Kelleher (1966).

Second-Order Schedules of Drug Injection

Figure 1 shows a cumulative record of performance of a squirrel monkey under a second-order schedule of cocaine injection where each 30th response produced a 2-second visual stimulus (FR-30:S) and the first FR-30 completed after the lapse of a 5-minute interval produced the stimulus change accompanied by an injection of cocaine. Each presentation of the 2-second visual stimulus is depicted in the record by a slash mark on the cumulative response curve; a 1-minute time-out that followed the injection is depicted by an offset of the lower event line. Each sequence of 30 responses was typically preceded by a pause and the longest pauses occurred early in the interval. Over the entire 5-minute interval, there was a pattern of positive acceleration of responding up to the cocaine injection. This pattern of responding is similar to that obtained with other drugs (Goldberg & Tang, 1977) and other nondrug reinforcing events (Barrett, Katz, & Glowa, 1981; Goldberg, 1973).
 

 
Cumulative record under second-order schedule

Figure 1: Cumulative record of a performance of a squirrel monkey responding under a second-order schedule of cocaine injection during a portion of one experimental session. Abscissa: time; Ordinate: cumulative responses. Slashes on the cumulative record designate 2-second presentations of the visual stimulus that accompanied cocaine injection at the end of the fixed interval. The offset of the lower event line indicates the 1-minute time-out that followed each cocaine injection. The recording reset to base after each 1-minute time-out. S. R. Goldberg, unpublished data.
 

Under second-order schedules, the stimuli that ultimately accompany the drug injection can serve to maintain responding themselves as conditioned reinforcers. Kelleher (1958) first suggested that extended sequences of behavior maintained by conditioned reinforcing stimuli might be of practical importance in the study of drugs as reinforcers since the influence of the drug on subsequent behavior could be minimized. In addition to practical utility, second-order schedules have proven to be of use in establishing extended sequences of behavior in experimental animals that are in many ways analogous to extended sequences of behavior in human abusers involving procurement, preparation, and administration of drug. Moreover, the amounts of behavior maintained under second-order schedules are more in accord with observations in human drug abusers of significant portions of their daily activities involving drug-seeking or drug-oriented behavior (Goldberg & Gardner, 1981).

Effects of Drug Dose

Under all schedules of drug injection, the rates of responding maintained are dependent upon the dose of drug administered per injection. Figure 2 shows data from several studies on effects of cocaine dose per injection on response rates maintained under different schedules of cocaine injection. Under the FI 5-minute schedule, the first response after 5 minutes produced a cocaine injection followed by a 1-minute time-out period, and experimental sessions lasted until 15 injections were administered (Goldberg & Kelleher, 1976). Low doses maintained low rates of responding that were comparable to those maintained by vehicle. Higher rates were maintained by higher doses with the maximal rates maintained at a dose of 50 mg/kg/injection. At higher doses, rates of responding were below the maximum rate maintained. The lower response rates at the highest doses are often attributed to direct pharmacological effects of the drug on subsequent responding, since these doses also decrease rates of responding maintained by reinforcers other than drug injection (cf. Spealman & Kelleher, 1979).

Initial studies with second-order schedules (Goldberg, 1973) suggested that a wide range of doses maintained maximal rates of responding. Figure 2 also shows effects of cocaine dose on response rates maintained under an FI 5-minute (FR:S) second-order schedule of cocaine injection with the temporal parameters of the schedule similar to the FI 5-minute schedule. Under the second-order schedule, rates of responding were much higher than those maintained under the FI 5-minute schedule. Additionally, the range of doses that maintained high rates is noteworthy since under the FI 5-minute schedule, rates of responding were decreased below maximum at doses that maintained high rates under the second-order schedule (Goldberg, Kelleher, & Goldberg, 1981a). Possibly, the direct effect on response rate of accumulated cocaine from successive injections was in some manner modulated by the brief stimuli presented under the second-order schedule.

Although spacing injections apart and interposing time-out periods following injections each limit the degree to which direct pharmacological effects alter subsequent responding, with parameters typically employed direct effects are not entirely eliminated. One method of precluding direct effects of the consequent drug injection is to arrange the schedule parameters so that one or several injections are administered, but only at the end of the experimental session. Under schedules such as these, responding is maintained throughout a relatively long interval until a response produces the consequent injection ending the experimental session. Second-order schedules have been particularly useful under these conditions in maintaining responding over long periods of time up to the ultimate injection. In several studies (Goldberg & Tang, 1977; Kelleher & Goldberg, 1977; Goldberg et al., 1981a) in which the injections were administered only at the end of the session, response rates increased with dose of the drug and high rates were maintained at doses that decreased rates under schedules in which injections occurred repeatedly within sessions.
 

 
Effects of cocaine dose on rates of responding
Figure 2: Effects of dose of cocaine per presentation on average rates of responding maintained under different schedules of cocaine injection. Circles: fixed-interval 5-minute schedule with a 1-minute time-out following each injection and 15 injections per experimental session (squirrel monkeys S-467 and S-474). Adapted with permission from Goldberg and Kelleher, 1976. Triangles: second-order schedule, FI 5-minute (FR:S), with a 1-minute time-out following each injection and 15 injections per experimental session. Adapted with permission from Goldberg, Kelleher, and Goldberg, 1981a. Squares: second-order schedule, FI 60-min (FR:S), with 15 injections of cocaine spaced 2 seconds apart following the reinforced response concluding the experimental session. Adapted with permission from Goldberg, Kelleher, and Goldberg, 1981a. Abscissa: dose of cocaine per presentation, log scale. Ordinate: mean overall response rates. See individual studies for details of experimental procedures.
 

Figure 2 also shows effects of cocaine dose on responding maintained under an FI 60-minute (FR:S) schedule when the experimental session ended after the injection of cocaine. High rates were maintained at a dose of 1.5 mg/kg; higher doses would likely produce convulsions. In contrast under the FI 5-minute (FR:S) schedule when injections occurred throughout the session, response rates were well below the maximum at 0.4 mg/kg/injection (Goldberg et al., 1981a).

Stimulus Functions under Second-Order Schedules

Functions of brief stimuli presented under second-order schedules of drug injection and food presentation have been extensively reviewed (Goldberg & Gardner, 1981; Gollub, 1977) and here will be summarized only briefly. Figure 3 shows the effects on rates of responding of removing the brief stimuli entirely or of substituting a brief stimulus that is not paired with either cocaine or morphine (Goldberg, Spealman, & Kelleher, 1979). Responding was maintained under second-order schedules in which completion of an FR requirement produced a brief stimulus and the first FR completed after 10 minutes (cocaine) or 60 minutes (morphine) always produced an amber light accompanying the drug injection. For studies of nonpaired brief stimuli, a brief blue light followed completion of each FR, whereas an amber light accompanied the drug injection. For studies on omission of the brief stimuli, the only stimulus change was the brief amber light that accompanied injections. Omissions of the brief stimuli decreased response rates as has been shown in other studies (Goldberg et al., 1981a; Goldberg, Spealman, & Goldberg, 1981b; Goldberg & Tang, 1977; Katz, 1979). Similar results are obtained under second-order schedules with fixed-interval components (Katz, 1979; Kelleher & Goldberg, 1977).

One study (Goldberg et al., 1981a) compared effects of omission of the brief stimuli on responding under second-order schedules of food or cocaine presentation at two different parameter values. Under one schedule food was presented or drug was injected following the first FR unit completed after 5 minutes. Under the other schedule the interval value was 60 minutes and the session ended after food was presented or cocaine was injected. Removing the brief stimuli decreased rates of cocaine-maintained responding under either schedule but only decreased food-maintained responding under the schedule employing the 60-minute interval. These results suggest that the brief stimulus associated with cocaine injection has some properties that are distinct from those of brief stimuli associated with food presentation.

Studies in which nonpaired brief stimuli were substituted for paired brief stimuli have also shown decreases in response rates with nonpaired stimuli (see Figure 3; Goldberg, Spealman, & Kelleher, 1979). The decreases in rates, however, were smaller than those that occurred when the brief stimuli were removed entirely. Similar results were obtained under second-order schedules with fixed-interval components (Katz, 1979). The finding that nonpaired stimuli maintained rates of responding greater than those maintained with stimuli entirely eliminated is not surprising considering the similarity of the paired and nonpaired stimuli.

Comparisons of Drug-Maintained Responding
and Food-Maintained Responding

Several studies have compared responding maintained under second-order schedules of drug injection with that maintained under comparable schedules by other reinforcing events. Initial studies indicated that responding maintained under second-order schedules of cocaine injection was maintained at rates higher than those maintained by more conventionally used reinforcing events such as food presentation (Spealman & Goldberg, 1978). Therefore, it was of interest to determine whether the differences in responding maintained by cocaine and other reinforcing events were due to unique properties of cocaine as a reinforcer.
 

 
Rates of responding under second-order schedules
Figure 3: Rates of responding under second-order schedules of intravenous cocaine or morphine injection when the completion of every fixed-ratio component during a fixed interval produced either a paired or nonpaired brief stimulus or when brief stimuli were omitted altogether. Overall rates were calculated by dividing responses by total time elapsed; local rates were calculated by dividing responses by the time elapsed from the first to last response of each fixed-ratio component. Bars show average rates of responding during the last three sessions of each condition for individual monkeys; brackets show ranges. Each condition was studied for 5 to 20 consecutive sessions. Reprinted with permission from Goldberg, Spealman, and Kelleher, 1979. Copyright 1979 by Pergamon Press, Inc.
 

Differences between rates of responding maintained under second-order schedules of cocaine injection and food presentation were found initially in studies where injections were scheduled to recur within experimental sessions. There are a number of effects of repeated presentations of cocaine within sessions which may influence the rates of responding maintained by cocaine. Administration of cocaine can alter subsequent responding due to direct pharmacological effects of the drug on the output of behavior. These effects may become manifest as an increase or a decrease in rates of responding depending on the accumulated dose of cocaine. Additionally, it has been suggested that psychomotor stimulants, such as cocaine, increase the effectiveness of conditioned reinforcing stimuli (e.g., Hill, 1970; Robbins, 1975). Either of these effects of cocaine may better account for differences between cocaine-maintained responding and responding maintained by other events than the postulated unique reinforcing properties of cocaine.

Under second-order schedules in which all drug injections occur at the end of the experimental sessions, the responding maintained is not influenced by direct pharmacological effects of the drug since, with sessions conducted daily, the pharmacological effects have subsided by the next session. In comparisons of food-and cocaine-maintained responding under these schedules, rates of responding maintained by the two events were comparable (Goldberg et al., 1981a; Katz, 1979) suggesting that an effect of cocaine injection within experimental sessions is critical to the differences in rates of responding maintained by cocaine and food presentation. Further, pre-session injection of cocaine in monkeys responding under second-order schedules in which food presentation recurs throughout sessions increases rates of responding to rates comparable to those maintained by cocaine when cocaine injections recur throughout sessions (Goldberg et al., 1981a). Additionally, pre-session injection of cocaine has comparable effects on food-and cocaine-maintained responding when those reinforcing events occur only at the end of experimental sessions (Valentine, Katz, Kandel, & Barrett, 1983). Thus, it appears that the differences in rates of responding maintained by cocaine injection and food presentation under second-order schedules are due to a pharmacological effect of cocaine rather than a unique property of cocaine as a reinforcer. Moreover, the increases in response rates produced by cocaine are comparable regardless of whether responses produce brief stimuli (Goldberg et al., 1981a). Therefore, it appears that the differences in rates of responding maintained by cocaine injection or food presentation are due to the direct effects of cocaine on rates of subsequent responding rather than a potentiation of the reinforcing effectiveness of the brief stimuli.

That under specific schedule conditions behavior maintained by disparate events such as food delivery or drug injection can be similar has several implications for the experimental study of drug abuse and also for psychology in general. In developing performances maintained by drug injections, conditions are arranged that minimize or preclude effects of the injection other than reinforcing effects. A major part of the development of procedures for maintaining behavior with consequent drug injections has been eliminating or minimizing these other effects of drug injections. In studies with more conventional reinforcers, such as food presentation, the procedures that have evolved are those under which other effects of the reinforcer are minimal. For example, the amount of food presented is typically so small that significant changes in the degree of deprivation of the subject do not occur within the experimental session. In general, the conditions under which any event can be suitably used as a reinforcer in laboratory studies depends on eliminating effects other than reinforcing effects that can influence subsequent responding (Morse, 1975). For the most part it is the other effects of a consequent event that make its use as a reinforcer unique. When these other effects are precluded, reinforcing effects of diverse stimuli can be observed to be quite similar. That diverse consequent events can control behavior similarly indicates that the performances maintained have an integrity that transcends the particular reinforcer employed and, moreover, that the schedules under which those events are presented are of critical importance in determining the performances maintained.

Implications of Performances under Second-Order Schedules for Assessing the Reinforcing Properties of Abused Drugs

The importance of the schedule under which drugs are presented in the behavioral analysis of drug abuse cannot be over emphasized. Under some schedules a drug may be readily self-administered whereas under other schedules it may not be. Thus, questions about the reinforcing strength or efficacy of a particular drug are more profitably couched as questions about the conditions under which that drug will function as a reinforcer. Some investigators have attempted to rank order drugs as to their reinforcing efficacy (e.g., Griffiths, Brady, & Bradford, 1979). However, the rank order of the reinforcing effectiveness of particular drugs would be limited to the conditions studied and of little real applicability.

Some have considered the range of conditions under which a drug will function as a reinforcer as an indication of the reinforcing efficacy of a drug; the assumption being that those drugs that maintain behavior over a more varied range of conditions are more effective reinforcers. Nicotine can both maintain behavior and punish behavior (Goldberg & Spealman, 1982) and, historically, maintenance of behavior by nicotine injection has been difficult to demonstrate in the laboratory (Henningfield & Goldberg, 1983). In contrast, cocaine has been studied as a reinforcer over a wide range of conditions in laboratory studies. However, a conclusion that cocaine is a drug of greater abuse potential than nicotine would stand in marked contrast with epidemiological studies of incidence of use of each of these drugs. Moreover, the rank order of reinforcing efficacy of a drug also has minimal therapeutic significance. A patient abusing a particular drug is given little comfort, and no better prognosis, by the knowledge that the drug is only self-administered under a limited range of conditions in experimental animals. Useful information is provided by studies that determine the conditions under which a drug maintains behavior and how changes in environmental conditions affect the behavior maintained.

The similarity of behaviors controlled by drugs and other consequent events brings into question tacit assumptions that apply to drugs as reinforcers (Morse, 1975). For example, it was noted above that the all-encompassing nature of drug-seeking and drug-oriented behaviors in human drug abusers suggested theories of abuse that emphasized pathology of personality or motivation of the drug abuser. Subsequently, experimental questions of whether drugs were unique as reinforcing stimuli were asked. Extended sequences of behavior under second-order schedules have been established in laboratory animals that are analogous to drug-seeking behaviors of human abusers. These behaviors resemble human drug seeking in that the subject engages in substantial amounts of activity and does virtually nothing else over extended periods of time.

Importantly, these extended sequences of behavior maintained by drug injection also resemble extended sequences of responding maintained by other reinforcers. These similarities emphasize that the all-consuming nature of drug-seeking and drug-taking is not the result of unnatural or pathological features of the drug abuser. Rather, these behaviors are the result of reinforcement by drug in an environment that controls behavior via natural processes such that drug related behavior becomes all but the exclusive activity of the subject. The "compulsive" gambler and overeater are analogous cases under the control of different reinforcing events. Under certain environmental conditions, events such as drug taking, overeating, or gambling may come to control unusual amounts of behavior, possibly because other effects that interfere with continued engagement in those activities are minimized. Under these conditions the normal sources of the "pathological" behavior reside in the unusual environment that creates conditions suitable for the maintenance and control of excessive amounts of behavior.

References

Barrett, J. E., Katz, J. L., & Glowa, J. R. (1981). Effects of d-amphetamine on responding of squirrel monkeys maintained under second-order schedules of food presentation, electric shock presentation or stimulus-shock termination. Journal of Pharmacology and Experimental Therapeutics, 218, 692-700.

Goldberg, S. R. (1973). Comparable behavior maintained under fixed-ratio and second-order schedules of food presentation, cocaine injection or d-amphetamine injection in the squirrel monkey. Journal of Pharmacology and Experimental Therapeutics, 186, 18-30.

Goldberg, S. R., & Gardner, M. L. (1981). Second-order schedules: Extended sequences of behavior controlled by brief environmental stimuli associated with drug self-administration. In T. Thompson & C. E. Johanson (Eds.), Behavioral pharmacology of human drug dependence (National Institute on Drug Abuse Research Monograph 37, pp. 241-270). Washington, DC: U.S. Government Printing Office.

Goldberg, S. R., & Kelleher, R. T. (1976). Behavior controlled by scheduled injections of cocaine in squirrel and rhesus monkeys. Journal of the Experimental Analysis of Behavior, 25, 93-104.

Goldberg, S. R., Kelleher, R. T., & Goldberg, D. M. (1981a). Fixed ratio responding under second-order schedules of food presentation or cocaine injection. Journal of Pharmacology and Experimental Therapeutics, 218, 271-281.

Goldberg, S. R., & Spealman, R. D. (1982). Maintenance and suppression of behavior by nicotine injections in squirrel monkeys. Federation Proceedings, 41, 216-220.

Goldberg, S. R., Spealman, R. D., & Goldberg, D. M. (1981b). Persistent high-rate behavior maintained by intravenous self-administration of nicotine. Science, 214, 573-575.

Goldberg, S. R., Spealman, R. D., & Kelleher, R. T. (1979). Enhancement of drug-seeking behavior by environmental stimuli associated with cocaine or morphine injections. Neuropharmacology, 18, 1015-1017.

Goldberg, S. R., & Tang, A. (1977). Behavior maintained under second-order schedules of intravenous morphine injection in squirrel and rhesus monkeys. Psychopharmacology, 51, 235-242.

Gollub, L. R. (1977). Conditioned reinforcement: Schedule effects. In W. K. Honig & J. E. R. Staddon (Eds.), Handbook of operant behavior (pp. 288-312). Englewood Cliffs, NJ: Prentice-Hall.

Griffiths, R. R., Brady, J. V., & Bradford, L. D. (1979). Predicting the abuse liability of drugs with animal drug self-administration procedures: Psychomotor stimulants and hallucinogens. In T. Thompson & P. B. Dews (Eds.), Advances in behavioral pharmacology (Vol. 2, pp. 163-208). New York: Academic Press.

Henningfield, J. E., & Goldberg, S. R. (1983). Nicotine as a reinforcer in human subjects and laboratory animals. Pharmacology Biochemistry & Behavior, 19, 989-992.

Hill, R. T. (1970). Facilitation of conditioned reinforcement as a mechanism of psychomotor stimulation. In E. Costa & S. Garattini (Eds.), Amphetamines and related compounds (pp. 781-795). New York: Raven Press.

Katz, J. L. (1979). A comparison of responding maintained under second-order schedules of intramuscular cocaine injection or food presentation in squirrel monkeys. Journal of the Experimental Analysis of Behavior, 32, 419-431.

Kelleher, R. T. (1958). Fixed-ratio schedules of conditioned reinforcement with chimpanzees. Journal of the Experimental Analysis of Behavior, 1, 281-289.

Kelleher, R. T. (1966). Chaining and conditioned reinforcement. In W. K. Honig (Ed.), Operant behavior: Areas of research and application (pp. 160-212). New York: Appleton-Century-Crofts.

Kelleher, R. T. (1975). Characteristics of behavior controlled by scheduled injections of drugs. Pharmacological Reviews, 27, 307-323.

Kelleher, R. T., & Goldberg, S. R. (1977). Fixed-interval responding under second-order schedules of food presentation or cocaine injection. Journal of the Experimental Analysis of Behavior, 28, 14-24.

Kelleher, R. T., & Morse, W. H. (1968). Determinants of the specificity of behavioral effects of drugs. Ergebnisse der Physiologie Biologischen Chemie und Experimentellen Pharmakologie, 60, 1-56.

Morse, W. H. (1975). Introduction: The control of behavior by consequent drug injections. Pharmacological Reviews, 27, 301-305.

Pickens, R., & Thompson, T. (1968). Cocaine-reinforced behavior in rats: Effects of reinforcement magnitude and fixed-ratio size. Journal of Pharmacology and Experimental Therapeutics, 161, 122-129.

Robbins, T. W. (1975). The potentiation of conditioned reinforcement by psychomotor stimulant drugs: A test of Hill’s hypothesis. Psychopharmacologia, 45, 103-114.

Sidman, M. (1960). Normal sources of pathological behavior. Science, 132, 61-68.

Sidman, M., & Stebbins, W. C. (1954). Satiation effects under fixed-ratio schedules of reinforcement. Journal of Comparative and Physiological Psychology, 47, 114-116.

Smith, R. F., Gustavson, C. R., & Gregor, G. L. (1972). Incompatibility between the pigeon’s unconditioned response to shock and the conditioned key-peck response. Journal of the Experimental Analysis of Behavior, 18, 147-153.

Spealman, R. D., & Goldberg, S. R. (1978). Drug self-administration by laboratory animals: Control by schedules of reinforcement. Annual Review of Pharmacology and Toxicology, 18, 313-339.

Spealman, R. D., & Kelleher, R. T. (1979). Behavioral effects of self-administered cocaine: Responding maintained alternately by cocaine and electric shock in squirrel monkeys. Journal of Pharmacology and Experimental Therapeutics, 210, 206-214.

Valentine, J. O., Katz, J. L., Kandel, D. A., & Barrett, J. E. (1983). Effects of cocaine, chlordiazepoxide, and chlorpromazine on responding of squirrel monkeys under second-order schedules of IM cocaine injection or food presentation. Psychopharmacology, 81, 164-169.

Woods, J. H., & Schuster, C. R. (1971). Opiates as reinforcing stimuli. In T. Thompson & R. Pickens (Eds.), Stimulus properties of drugs (pp. 163-175). New York: Appleton-Century-Crofts.


©1987 Springer-Verlag (printed version)
©2000-2009 Addiction Science Network (web-enhanced version)



ASNet Home

ASNet Profile

Illicit Drug Index

Virtual Lab Tour

Research Reports

Drug Classification

A Primer on Drug Addiction

Experimental Methods

Treatment Resources

Biological Basis of Addiction

Before Prohibition: Early Psychoactive Medicines

Links to Other Websites

Click here to enter the Addiction Science Network Discussion Forum

Brain Reward System©1999-2009 Addiction Science Network
This page was last revised 05 April 2009 13:21 EDT.
Send comments to: feedback@AddictionScience.net
Report technical problems to: webmaster@AddictionScience.net