A Brief Note

Research on operant behavior originated in the field of the psychology of learning. However, its application has fostered the flourishing of various disciplines, such as behavioral pharmacology. Studies incorporating operant behavior are also expanding into the realms of neuroscience and brain science. There is significant scientific importance in elucidating both learning behavior—as the overt, final expression of an organism integrating processes at genetic, molecular biological, biochemical, and physiological levels—and the underlying brain mechanisms that drive it.

Skinner, B.F. conducted experimental research on operant behavior, mainly using rats and pigeons, in the psychology laboratory of Harvard University. Based on this, he constructed a system of reinforcement theory as a basic principle of behavior. From the moment of birth, living organisms exhibit various spontaneous behaviors (responses), which are subject to stimulus feedback from the environment. Only stimulus feedback that is suitable for the survival of the organism reinforces the behavior, and the frequency of the behavior increases and becomes established. This is the learning principle of the organism, and also the essence of reinforcement theory. In this case, the behavior itself, whether human or animal, is the subject of empirical scientific research, and there is no perspective of exploring the mind of an animal through its behavior. However, the Skinner school does not deny the awareness of the problem of understanding important issues such as the mind and consciousness of humans, which exist on the other hand. Historically, psychology has taken up many issues of the mind, but in the end it was not accepted as a research field in the natural sciences, and the perspective of the Skinner school has greatly changed this. The reinforcement theory of biological behavior is an objective scientific viewpoint that leaves no room for so-called subjective psychologism, and the aspect of reinforcement behavior, therefore, has been adopted in the field of neuroscience, where its usefulness has been demonstrated.

This position is believed to lead to an essential understanding of human behavior that avoids fruitless theological debates and spiritualism. The study of this field is called the Experimental Analysis of Behavior, and is an academic system that includes both methodological ideas based on a scientific observational viewpoint on behavior and actual behavior control techniques.

The academic system and techniques based on the experimental analysis of operant behavior built by the Skinner school are widely applied to many fields other than neuroscience, including behavioral pharmacology, drug dependence (addiction) studies, education, economics, and many others, demonstrating the universality and usefulness of this academic system.

The following URL is a description of Skinner on the homepage of the Department of Psychology at Harvard University.

https://psychology.fas.harvard.edu/people/b-f-skinner

Photo from Animal Behavior, Life Nature Library, 1966.

The followings are some reference books on operant behavior.

1) Holland, J.G. and Skinner B.F.: The Analysis of Behavior, A Program for Self-Instruction. McGraw Hill Book Company, Inc. 1961.

The above is one of the most appropriate textbooks for understanding operant behavior. This book is structured to be read by program learning, and each piece of knowledge and concept is learned properly before moving on to the next step. It is different from normal reading, where you read the pages whether you understand it or not. As you read this book, you will realize that your reading behavior is supported by the principles of operant behavior, and after reading, you will be left with a refreshing sense of accomplishment. Although it is a textbook from more than half a century ago, you can properly learn the basics of operant behavior science. In the latest fields of medicine and biology, such as genetic engineering, molecular biology, and immunology, old textbooks may have historical significance, but they may not be sufficient to absorb correct knowledge. In these fields, research subjects are broken down into individual elements and thoroughly analyzed/clarified, which can lead to major changes in previous concepts. On the other hand, behavioral science research is also advancing day by day, but the idea of ​​behavior, the most advanced and integrated functional framework of living organisms, will not change as long as it is correct. This is why I believe the above textbooks have not faded.

2) Skinner B. F.: The Behavior of Organisms: An Experimental Analysis. 1938, Appleton & Century, Reprinted by the B. F. Skinner Foundation in 1991 and 1999.

The above is called the bible of operant behavior. It takes some effort to read the whole thing. More than 85 years ago, the young Skinner published a book that included the contents of his dissertation at Harvard University.

Of particular note is the description of his joint research with W.T. Heron near the end of the book. Specifically, he describes the effect of caffeine and bezedrine (amphetamine) in increasing the lever-pressing operant behavior of rats. He particularly notes that amphetamine increases the lever-pressing response to obtain food, despite its appetite suppressing effect. About 30 years later, mainly in the United States, a new academic field called behavioral pharmacology, which encompasses knowledge of drugs and operant behavior, blossomed.

3) Masaya Sato: Operant Behavior and Experimental Behavioral Analysis - The History and Future of the Twins - Psychology Review, Vol. 18, No.3, 129-161, 1975 (in Japanese).

3)  佐藤方哉：オペラント行動と実験行動分析学 -その双生児の来し方行末 -   心理学評論 1975年 Vol. 18 No.3, 129-161

A historical overview of the research achievements of the Skinner school and its future are thoughtfully written in Japanese. The PDF in Japanese can be viewed at the following URL.

https://www.jstage.jst.go.jp/article/sjpr/18/3/18_129/_pdf/-char/en

See Drug Dependence and Behavioral Analysis in this WEB site

It is well known that animals press levers stably and frequently to obtain food pellets, etc., as operant behavior. The above photo shows a rat in an operant experimental chamber (Skinner box) with two levers. As examples, two types of discriminative operant behaviors are explained here. One is light-dark discrimination behavior, in which the animal is cued by an external sensory stimulus related to the presence or absence of a light, and the other is drug discrimination behavior, in which the animal is cued by an internal sensation brought about by drug administration (photo from the authors' experiment).

Light-dark discrimination behavior related to the presence or absence of a light:

One of the lights on the two levers is randomly lit for each trial. The rat's lever-pressing response on the lit side is reinforced with food pellet, and the lever-pressing response on the unlit side is not reinforced. This training is repeated. As a result, the rat comes to press only the lever on the lit side with almost 100% accuracy, and thus, the light-dark discrimination behavior is established. When the optimal dose of the central acetylcholine nerve inhibitor scopolamine is administered subcutaneously to these rats, the correct selection rate decreases from 100% to the chance level of 50%. At this time, the total number of correct and incorrect responses is not significantly different from that of the saline control. This shows that this experiment did not simply detect the nonspecific inhibitory effect of the drug, but rather detected a specific impairment effect of the drug on the light-dark discrimination behavior because only the perccent correct responses decreased without changing total number of responses. For this reason, if light-dark discrimination behavior is considered a simple experimental system for measuring cognitive function, this behavior can be used as an animal model for measuring cognitive dysfunction caused by drugs.

Hironaka N, Miyata H, Ando K (1992) Effects of psychoactive drugs on short-term memory in rats and rhesus monkeys. Japanese Journal of Pharmacology. 59(1): 113-120.

 https://doi.org/10.1254/jjp.59.113

Discrimination behavior for the internal sensory effects of drugs:

For drug discrimination behavior, the two-lever experimental condition is the same as above. However, in this case, external sensory stimuli such as a lighted lamp are not used as a discrimination cue. However, the experimental setup is such that the animals sense the effects of the administered drug and use them as a discrimination cue. For example, a rat is reinforced with food only for pressing the left lever out of two levers after subcutaneous administration of methamphetamine at a certain dose. On another day, the rat is reinforced with food only for pressing the right lever after subcutaneous administration of saline. By repeating this kind of training, the rat will be able to discriminate the difference in internal sensations after methamphetamine and saline administration based on the difference in left and right lever pressing responses. From this, it can be concluded that the rats discriminating the effect of methamphetamine as an internal sensation different from that of saline administration. This method is a useful animal experimental method for investigating the subjective effects of drug administration in humans. The subjective effects of drugs are deeply related to the formation of psychic dependence on drugs, and are methodologically closely linked to the intravenous drug self-administration experiment using laboratory animals described later.

Ando K, Yanagita T (1992) Effects of an antitussive mixture and its constituents in rats discriminating methamphetamine from saline. Pharmacology, Biochemistry and Behavior, 41(4): 783-788.

https://www.sciencedirect.com/science/article/abs/pii/0091305792902277

Ando K, Hironaka N (1991) Behavioral pharmacological studies on LY127809. Preclinical Reports of the Central Institute for Experimental Animals, 17 (1) :1-14 (Text in Japanese with tables, figures and abstract in English).

安東潔，廣中直行 (1991)    ラットにおける LY127809 の行動薬理試験。実中研・前臨床研究報, 19 (2) :73-92..

https://researchmap.jp/read0179769/published_papers/51530391

LY127809: Dopamine agonist; Anti Parkinson's dieaese drug

Other papers by the author using rat operant behavior

Ando K (1975) The discriminative control of operant behavior by intravenous administration of drugs in rats. Psychopharmacologia (Berl), 45: 47-50.

https://link.springer.com/article/10.1007/BF00426208

Ando K (1975) Profile of drug effects on temporally spaced responding in rats. Pharmacology, Biochemistry and Behavior, 3(5): 833-841.

https://www.sciencedirect.com/science/article/abs/pii/0091305775901148

In the small monkey common marmoset, in an operant box with two levers, pressing the lever on the side where a light is on is reinforced with juice. Lever-pressing operant behavior in marmosets can be formed to some extent. However, compared to rats and rhesus monkeys, it is thought that the behavior is not stable. The reason for this is that it is difficult to impose water or food deprivation as severe as those of rats and rhesus monkeys in order to increase motivation to press the lever. This is to avoid weakening this small monkey, which is not physically tough. In addition, marmosets have behavioral characteristics that react sensitively to various stimuli and lack composure. For these reasons, The author has the impression that marmosets do not establish a stable operant behavior baseline like rats and rhesus monkeys.

In preclinical medical research, the evaluation of drug effects is premised on the establishment of a stable baseline behavior in laboratory animals, so the author has personally become cautious about using marmosets in this field. However, it will be important to accumulate more knowledge about marmosets' learning behavior and make an objective evaluation of this issue (photo from the authors' experiment).

2.3. Audiovisual stimulus-reinforced operant behavior in common marmosets

(based on touch responses to videos on a tablet (iPad) screen)

Taking advantage of the marmoset's sensitive response to various stimuli, we simultaneously presented nine videos of monkeys on an iPad screen in silence and formed a touch response to one of them. The reinforcing stimuli for this response were an enlargement of the video of the monkey that was touched and the sound of the monkey's cry. Under these conditions, the marmoset was able to establish a screen-touch response. This behavior can be considered to be based on sensory reinforcement or audiovisual reinforcement, and is a learned behavior that was established even without using food or juice as a reinforcing stimulus (photo from the authors' experiment).

Ando K, Inoue R, Haga H, Nishime C, Nishinaka E, Urano K (2025) Tablet screen-touch behavior with audiovisual stimulus consequences in the common marmoset (Callithrix Jacchus). International Journal of Comparative Psychology, 38: 1-16.

https://escholarship.org/uc/item/06k3f6x5#article_main

Three circular stimulus boards were attached to the wall panel in an individual living cage for rhesus monkeys. Each of these stimulus boards was connected to a touch sensor, and the monkey's touch response to the stimulus board was recorded one by one. The central stimulus board was used to present the sample stimulus, and either red or blue was lit for each trial. After a certain time had passed since the central stimulus board was turned off, the left and right choice stimulus boards were presented with either red or blue, in a random left-right arrangement for each trial. The touch response of the choice stimulus board with the same color as the previously presented sample stimulus was reinforced with orange juice. Through repeated training, the monkeys responded to the choice stimulus of the same color as the sample stimulus even after a certain time had passed since the sample stimulus was turned off, and the correct choice response rate was consistently over 80%. Since there is no external clue for such a correct choice response, it is thought that even animals form some kind of memory trace related to color in their brains and use it as a clue. This model is used for preclinical medical research evaluations of treatments for memory disorders (photo from the authors' experiment).

Ando K, Hironaka N, Shuto K (2003) Effects of vinconate on scopolamine-induced memory impairment in rhesus monkeys. Japanese journal of neuropsychopharmacology, 23(1): 43-46.

https://www.researchgate.net/publication/10808352_Effects_of_vinconate_on_scopolamine-induced_memory_impairment_in_rhesus_monkeys

Other papers by the authors using rhesus monkey operant behavior:

Ando K, Johanson CE, Schuster CR (1987) The effects of ethanol on eye tracking in rhesus monkeys and humans. Pharmacology, Biochemistry and Behavior, 26(1): 103-109.

https://pubmed.ncbi.nlm.nih.gov/3562482/

Ando K, Johanson CE, Schuster CR (1986) Effects of dopaminergic agents on eye tracking before and after repeated methamphetamine. Pharmacology, Biochemistry and Behavior, 24(3): 693-699.

https://www.sciencedirect.com/science/article/abs/pii/0091305786905769

Ando K, Johanson CE, Seiden LS, Schuster CR (1985) Sensitivity changes to dopaminergic agents in fine motor control of rhesus monkeys after repeated methamphetamine administration. Pharmacology, Biochemistry and Behavior, 22(5): 737-743.

https://sites.google.com/d/1OXDJ12xGrdLOX-F9gxmIrZEHUXDPOUeS/p/1jSXLxfOr08mAcUy6GzigDw4GlKuN4Eao/edit

Ando K, Johanson CE, Levy DL, Yasillo NJ, Holzman PS, Schuster CR (1983) Effects of phencyclidine, secobarbital and diazepam on eye tracking in rhesus monkeys. Psychopharmacology (Berl), 81(4): 295-300.

https://link.springer.com/article/10.1007/BF00427566

Ando K, Takada K (1979) Trialwise tracking method for measuring drug-affected sensory threshold changes in animals. Neurobehavioral Toxicology, 1 (Suppl 1): 45-52.

https://pubmed.ncbi.nlm.nih.gov/299584/

Ando K, Yanagita T (1978) The discriminative stimulus properties of intravenously administered cocaine in rhesus monkeys. In Colpaert, F and Rosecrans, J Eds. Stimulus Properties of Drugs: Ten Years of Progress. Elsevier/North-Holland pp. 125-136.

https://researchmap.jp/read0179769/published_papers/6895107

When a rat presses a lever, it receives a weak electric current at a specific site in the brain. When the appropriate site in the basal ganglia is stimulated, the rat will press the lever frequently. This has revealed the existence of a site in the brain called the self-stimulation-reward system. This type of reinforcement behavior is something that animals would never encounter in the wild, and in this respect it is fundamentally different from reinforcement behaviors such as food and juice. However, it has something in common with food and juice in that it is a positive reinforcement behavior in which the rat actively seeks a specific stimulus. For the difference between "reward and reinforcement," please refer to the page on  Drug Dependence and Behavioral Analysis .

Figure from Psychobiology: The Biological Bases of Behavior, Animal Behavior, Readings from Scientific American, 1966, W.H. Freeman & Company.

For images of the experimental animals treated as above, please refer to the bottom of this page, "4. Ethics of Animal Experimentation."

Olds J (1958) Self-stimulation of the brain. Science, 127 (3294): 315-324.

http://dx.doi.org/10.1126/science.127.3294.315

When the rat presses the lever, a fixed unit dose of drug (e.g., morphine) is infused intravenously through a catheter. Using this method, it has been shown that rats will voluntarily take drugs known to be dependence potential in humans. This method is considered a standardized experimental method for predicting human psychic dependence potential of drugs in rats. This behavior, like the intracranial self-stimulation behavior described above, is a positive reinforcement behavior that animals do not encounter in the natural world and can only be observed in an experimental setting.

Figure from Psychobiology: The Biological Bases of Behavior, Animal Behavior, Readings from Scientific American, 1966, W.H. Freeman & Company.

For images of the experimental animals treated above, please refer to the bottom of this page, "4. Ethics of animal experiments."

Weeks, J (1962) Experimental morphine addiction: Method for automatic intravenous injections in unrestrained rats. Science, 138 (3537): 143-144.

https://www.science.org/doi/10.1126/science.138.3537.143

See this website: Concept of drug dependence & Drug dependence and behavioral analysis

Intravenous drug self-administration experiments were also conducted on rhesus monkeys. Even now, it is possible to conduct such experiments if there is a clear medical and biological research purpose, but sufficient consideration must be given to animal ethics. This method using rhesus monkeys, whose brains are highly developed and whose drug sensitivity is extremely similar to that of humans, has scientifically shed light on the problem of drug dependence behind drug abuse in humans. Drug abuse is an extremely serious problem both personally and socially. This method using rhesus monkeys makes it possible to predict the presence and degree of psychic dependence of new compounds in humans much more accurately than rats. The highly valid scientific facts obtained here are used as important scientific experimental data in determining legal regulations regarding drug use with the aim of preventing drug abuse in humans. 

Dr. Tomoji Yanagida (1930-2016), who developed this method at University of Michigan in the United States, opened the Preclinical Medicine Research Institute after returning to Japan, which at the time was one of the central centers of drug dependence research in Japan and around the world (see this website: Drug Dependence Concept & Drug Dependence and Behavioral Analysis ).

Photo from Psychobiology: The Biological Bases of Behavior, Animal Behavior, Readings from Scientific American, 1966, W.H. Freeman & Company.

For images of the experimental animals treated as above, please refer to the bottom of this page, "4. Ethics of Animal Experiments."

Denau G, Yanagita T, Seevers M (1969) Self-administration of psychoactive substances by the monkey. Psychopharmacologia, 16 (1): 30-48.

http://dx.doi.org/10.1007/BF00405254

安東潔，川口武，柳田知司： アカゲザルおよびラットにおける LY127809 の依存性試験。実中研・前臨床研究報，1993, 17 (1) :55-81.

https://researchmap.jp/read0179769/published_papers/51530488

LY127809: Dopamine agonist; 抗パーキンソン病薬

安東潔，柳田知司： アカゲザルにおける LY127809 の依存性追加試験。実中研・前臨床研究報，1993, 19 (1) :1-10.

https://researchmap.jp/read0179769/published_papers/51530513

LY127809: 上記参照

Ando K, Kawaguchi T, Kawakami Y, Yanagida T (1993) Dependence study on LY170053 in rhesus monkeys and rats. Preclinical Research Reports of the Central Institute for Experimental Animals, 19 (2):73-92 (Text in Japanese with tables, figures and abstract in Englishn).

安東潔，川口武，河上喜之，柳田知司 (1993)    LY170053 のアカゲザルおよびラットにおける薬物依存性試験。実中研・前臨床研究報, 19 (2) :73-92.

https://researchmap.jp/read0179769/published_papers/51524747

LY170053: Olanzapine or Zyplexa; atypical antipsychotic, bipolar disorder treatment, antiemetic.

Ando K, Kawaguchi T (1997) Dependence study on SM-9018 in rhesus monkeys and rats. Basic and Clinical Studies, 31 (2): 321-341  (Text in Japanese with abstract, tables and figures in English).

安東潔，川口武 (1997)    SM-9018 のアカゲザルおよびラットにおける薬物依存性試験。基礎と臨床, 31 (2): 321-341.

https://researchmap.jp/read0179769/published_papers/51397707?lang=en

SM-9018: Perospirone, an antipsychotic drug.

Rhesus monkeys in their individual living cages formed the behavior of voluntarily inhaling cigarette smoke. Initially, the sucking behavior from a metal pipe was induced by orage juice. Next, the behavior was gradually replaced by cigarette smoke, and finally, spontaneous suking behavior was formed in response to cigarette smoke without orange juice. The smoking device was designed so that when the monkey smoked the pipe, the cigarette was automatically lit upon detection, allowing the monkey to spontaneously inhale cigarette smoke at any time 24 hours a day. Observation of the monkeys' voluntary smoking behavior in this way experimentally clarified that the factor that maintains smoking behavior is nicotine in cigarette smoke, and various environmental factors that affect smoking behavior (photo from the authors' experiment).

For photos of the experimental animals above, please refer to the bottom of this page, "4. Ethics of Animal Experiments."

Ando K, Yanagita T (1981) Cigarette smoking in rhesus monkeys. Psychopharmacology (Berl), 72 (2): 117-1127.

https://link.springer.com/article/10.1007/BF00431644

https://researchmap.jp/read0179769/published_papers/3506731

Ando K, Hironaka N, Yanagita T (1986) Development of cigarette smoking in rhesus monkeys. In Harris, LS., ed. Problems of Drug Dependence 1985. National Institute on Drug Abuse Research Monograph 67: DHHS Pub. No. (ADM) 86-1448. Washington, DC: Supt. of Docs., U.S. Govt. Print. Off., 1986. pp. 147-153.

https://pubmed.ncbi.nlm.nih.gov/3092061/

https://researchmap.jp/read0179769/published_papers/3506742

See other pages in this website: Drug Dependence Concept & Drug Dependence and Behavioral Analysis

3. Principles of the formation of learning behavior

4. Ethics of Animal Experimentation

Research using laboratory animals has a clear scientific or medical purpose, and is premised on conducting the experiment under conditions that consider animal ethics. Currently, in Japan, animal experiments are required to be conducted in accordance with the "Law for the Protection and Management of Animals." The spirit of this is based on the 3 R principle as shown in the figure above. That is, Reduction (reducing the number of animals used as much as possible), Replacement (not using live animals if possible, and replacing them with other methods such as cells), and Refinement (minimizing pain and suffering of animals). Whether or not research is actually conducted under these conditions is the responsibility of each facility, and strict review of the research plan is conducted by the Animal Experiment Ethics Committee, etc. Animal experiments must be conducted only after passing such review and approval by the facility.

It has been a long journey to get to this point, and it is true that there have been animal experiments in the past that were completely unacceptable. In the research on operant behavior conducted by B. F. Skinner, positive reinforcing stimuli such as food were mainly used. To form learning behavior, avoidance learning behavior against negative reinforcing stimuli such as electric shock can also be formed. Skinner has consistently argued that positive reinforcement, not negative reinforcement, should be used to educate humans. He even wrote a novel called Walden 2 about an ideal society that would be based solely on positive reinforcement.

The above-mentioned brain self-stimulation experiment involves surgical procedures such as implanting electrodes in the brains of animals. However, research based on this experiment has revealed the existence of a reward system in the brain. This is extremely significant in elucidating the mechanisms of the brain. In addition, the intravenous self-administration experiment is extremely important in evaluating the psychic drug dependence property or potential of medicines and drugs in humans. The results of research based on this experiment provide a scientific basis for determining restrictions on the use of dependence drugs in humans. This plays a major role in preventing drug abuse in society. In particular, if you refer to "7.7. The harsh reality of drug addiction and a drug-abusing society" on the page "Drug dependence concept" on this website, you will understand that targeted basic research on drug addiction is an urgent issue, along with several other measures that need to be taken (Drug Dependence Concept).

In addition, the smoking behavior experiment on monkeys induced voluntary smoking behavior similar to that of humans. This was significant in that it scientifically explored the factors that maintain smoking behavior and provided scientific data that will contribute to treatments such as smoking cessation, and we believe that there was a clear reason for conducting the animal experiment.