A Brief Note

Marmosets are highly valuable as laboratory animals—particularly among non-human primates—and are attracting significant attention for use in research related to brain and neuroscience.

Contents of this page

1. The common marmoset

The Common Marmoset (Callithrix Jacchus) has been attracting attention in recent years as an important experimental non-human primate (monkey). This monkey weighs about the same as a larger adult rat, and is small and easy to handle for a monkey. In addition, it is prolific, which is advantageous from the perspective of breeding experimental animals. There is also a low risk of serious zoonotic diseases, which is a concern for macaques such as rhesus monkeys and cynomolgus monkeys. From the above, it can be said that marmosets meet several important requirements as experimental animals (the photo above was taken by the author).

Marmosets are New World monkeys that originally live in wooded areas on the northeastern coast of Brazil in South America. Although their bodies are small, their brains are highly developed, and there are high expectations for their use in preclinical medical research on neuropsychiatric disorders and neuroscience studies. Of course, the same can be said for in vivo experimental medical research on physical disorders.

It was Dr. Tatsuji Nomura (1992-2013), founder and first director of the Central Institute for Experimental Medicine and Life Science (CIEM), who first noticed the potential of marmosets as experimental monkey animals and developed them into experimental animals. He imported the first 17 marmosets directly from South America to the Central Institute for Experimental Medicine and Life Science in 1973, more than 50 years ago (Nomura and Iinuma, 2008). At that time, nothing was known about marmosets as experimental animals, so the basic techniques and experimental techniques for raising and producing these monkeys as experimental animals had to be built from scratch, after many failures. In parallel, basic academic knowledge was also accumulated in physiology, including reproductive physiology, endocrinology, anatomy, blood biochemistry, pathology, etc. (Nomura and Iinuma, 1991). The person in charge of these actual tasks was Dr. Yoshikunu Tanioka (Tanioka, 1999).

At that time, CIEM used rhesus macaques (Macaca (M) mulatta), crab-eating macaques (M. fascicularis), Japanese macaques (M. fuscata), squirrel monkeys (Saimiri sciureus), and tamarins (Saguinus oedipus) as experimental primates for experiments or for evaluation of their usefulness as experimental animals. However, in the late 1990s, Director Tatsuji Nomura made the decision to focus on marmosets as the only monkey species at CIEM. Since then, in the early 2000s, all monkey species at CIEM have been marmosets.

Now, a quarter century later, the marmoset as an experimental animal has attracted attention worldwide (Servick, 2018). The US National Institute of Health (NIH) has published a white paper on the usefulness of marmosets as experimental animals, which contains specific and detailed descriptions of the usefulness and future prospects of this experimental animal (NIH 2019 Marmoset Community White Paper: URL: see the references section below). Below, we have listed the characteristics of marmosets as experimental animals, their usefulness/future potential, and our own experiences, in a category-based manner, with reference to the contents of this white paper.

2. Characteristics of marmosets as experimental animals

2.1. Small body size

Being the same size as a rat, marmosets require less space for breeding/laboratories. They are easy to handle as experimental animals, and less food, breeding equipment, drugs including therapeutic drugs, and expensive experimentally synthesized test compounds are required compared to macaques such as rhesus monkeys, which weigh more than 10 times as much, making them economically and practically advantageous.

2.2. Low level of aggressive behavioral characteristics

Marmosets are docile and weaker than aggressive macaques. Therefore, marmosets are easy to handle in breeding and experimental use. However, when breeding and using marmosets in experiments, handlers must wear special clothing and take sufficient precautions, such as using leather gloves when capturing them.

2.3. Low risk of serious zoonotic diseases

In macaque monkeys, the risk of serious zoonotic diseases such as herpes B virus and Marburg fever cannot be ignored. Marmosets have been artificially bred in hygienic and physically controlled rooms for decades, and the above risks are low. However, when handling marmosets in breeding laboratories, disposable hats, masks, overalls, gloves, and special footwear are required. This is to prevent two-way pathogenic infection between marmosets and humans. It is also important that the breeding and experimental environment is properly controlled in terms of hygiene and physical environment, just like during breeding.

2.4. High reproductive rate

Reproductive rate is an important condition for producing experimental animals. Although not as prolific as mice/rats, they are prolific monkeys. That is, a female marmoset gives birth to two or three pups twice a year starting two years after birth. Based on this assumption, a female will give birth to approximately 40 pups in her 10-year lifespan. In contrast, a female macaque will give birth to only a few pups in her lifetime.

2.5. Suitable for the introduction and development of gene modification technology

A high reproductive rate is advantageous for the introduction of gene modification technology. Based on the reproductive physiology of marmosets and the accumulated knowledge of gene modification technology for mice, attempts are being made to introduce human disease genes and other gene modifications in marmosets. The ultimate goal of these efforts is to establish a system in which such genetically modified marmosets can be put on the production line and steadily supplied to researchers as experimental animals.

2.6. Short life span

The lifespan of marmosets is usually around 10 years, although there are records of a maximum lifespan of 20 years. Within this scope, lifelong follow-up studies of individual marmosets will enable research into normal aging and diseases associated with aging. In other words, a five-year research project continued over two generations through a well-established experimental plan in the laboratory will provide meaningful data for the research topic. Diseases include Alzheimer's disease, dementia, Parkinson's disease, circulatory disorders, cerebrovascular disorders, hypertension, cancer, type 2 diabetes, chronic obstructive disease, muscle degeneration, osteoarthritis, osteoporosis, cataracts, macular degeneration, and hearing impairment.

2.7. Brain structure highly similar to humans

The structure, neural network, and neural function of the marmoset brain are common to those of macaque monkeys, and are similar to humans in some ways. Marmosets have a prefrontal cortex that rats and mice do not have, and there are areas of the brain that are thought to be related to higher motor functions, sensory functions, and cognitive functions (including social cognition). For this reason, marmosets are expected to be useful experimental animals for human brain research.

2.8. Advanced motor function

Marmosets, like macaques, have highly advanced motor functions. For example, fine motor control of the limbs, which is difficult to detect in rats/mice, can be observed in marmosets. In addition, when the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: MPTP) is administered subcutaneously to marmosets, Parkinson's disease-like syndrome, including limb tremors, can be observed in detail. Compared to before MPTP administration or normal marmosets, the motor dysfunction is clear and can be objectively quantified. Therefore, in marmosets, it is extremely easy and sensitive to determine whether or not a new compound has a therapeutic effect on this motor dysfunction (Ando et al., 2008, Ando, ​​2018). In this respect, marmosets are not only comparable to macaques in terms of determining whether or not a treatment is effective, but also have advantages over macaques. For more information, see the following URL: https://researchmap.jp/read0179769/published_papers/19447809

2.9. Mutual communication and social behavior

A wide variety of facial expressions, vocal communication, and various behavioral expressions are observed in social group situations in marmosets. In particular, the mutual behavior of marmosets in couples and between parents and young is distinctive. In addition to social communication, marmosets also respond sensitively to various external stimuli. This is thought to be due to the structure of the highly developed neocortex (prefrontal cortex, audiovisual cortex, etc.) of the marmoset brain, and there are hopes for the use of marmosets in neuroscience research in this area. For example, it was found that marmosets' touch response to a tablet (iPad) screen was reinforced by audiovisual stimuli without the use of reinforcing stimuli such as food or juice (see the following URL).

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

2.10. Structure and function of the visual and auditory organs

The existence of advanced visual and auditory organs is a prerequisite for the behaviors mentioned above (2.9). Marmosets have relatively large eye balls and excellent visual functions. However, they are not said to have the same color vision as humans or macaques. On the other hand, the frequency-threshold characteristic function (loudness curves such as Fletcher-Manson) of the hearing of marmosets is similar to that of macaques. The characteristics of macaques are said to be very close to the hearing characteristics of humans.

2.11. Homogeneity as an experimental animal

An important condition for experimental animals that underlies all of the above items is that marmosets have biological homogeneity. When conducting an experiment, it is common scientific practice to use several animals, take into account the variability of the data, and conduct and analyze whether there is a statistically significant difference between the control group and the experimental group. In this case, if the experimental animals used are not biologically homogeneous, the data will vary widely and clear conclusions may not be possible.

Marmosets as experimental animals have been bred and reared in a random, non-inbred system in a controlled, closed colony environment for over 40 years. Therefore, when using marmosets in experiments, a certain degree of biological homogeneity is guaranteed between each individual, which is a notable feature compared to other monkey species as macaques.

The late Dr. Tatsuji Nomura made efforts to realize the production and breeding of cloned marmosets with the same genetic information. If this is realized, it will be possible to go further than the biologically homogeneous experimental animals mentioned above and use a large number of genetically and biologically identical experimental animals in experiments. This is extremely significant in preclinical medical research and in vivo experimental medicine. Looking back at the history of animal experiments, there were many studies in which experimental data was highly variable and clear conclusions could not be drawn due to the use of wild mice and animals with unknown histories. Since then, experimental data has been greatly improved and its reliability has increased by using experimental animals with a clear lineage, such as rats and mice, which are homogeneous. Therefore, this trend will likely advance further by using experimental animals with the same genetic information.

3. Pioneers of marmoset neurobehavioral analysis research before 21 st century

As mentioned above, the common marmoset was first noticed as a useful experimental animal, and efforts to realize its use began in the 1970s, more than half a century ago. Since then, the preparation and research of the common marmoset as an experimental animal have progressed at a slow or steady pace. It was only in the 21st century that the pace accelerated. Therefore, within the narrow scope of the author's perspective, the author would record only the things that the author happened to notice about the neurobehavioral analysis research of marmosets that occurred before the year of 2,000.

First of all, in 1980, Stephan H et al. published a marmoset brain map by Springer-Verlag (Stephan et al., 1980). This is a specimen of the marmoset brain, with the main part divided into coronal sections at 0.5 mm intervals. Neurons were stained with cresyl fast violet or gallocyanine, and nerve fibers with iron hematoxyline. Currently, many marmoset brain maps have been published, including 3D high-field MRI and the latest staining techniques, but the above brain map is one of the pioneers.

The original paper on the Parkinson's disease model treated with the neurotoxin MPTP, which fully demonstrates the unique characteristics of marmosets, was published by Jenner et al. in 1987 (Jenner et al., 1987). Furthermore, Dr. Nomoto, who studied abroad at King's College in the UK and is also a co-author of the above paper, reported on the usefulness of marmosets in pharmacology and neurobehavioral analysis in the 1995 Japanese Pharmacology Journal (Nomoto, 1995). The full text of this paper is available in PDF format (see references below).

In 1997, Fukuoka T et al. published an original paper on haloperidol-induced movement disorders in marmosets in an international academic journal from Sumitomo Pharmaceuticals (Sumitomo Dainippon Pharma → Sumitomo Pharma) (Fukuoka et al., 1997).

There are many other points that should be mentioned, but we would like to express our respect for the achievements in neurobehavioral studies at a time when the usefulness of marmosets was not as clearly recognized as it is today, so we have listed some of them here.

4. Future use of the marmoset as a laboratory animal

Marmosets are expected to be useful experimental animals in neuroscience research, in vivo experimental medical research, preclinical medical research, and other fields, and are attracting attention. However, their usefulness has not been clearly understood, and they may  not be useful in all cases.

From my own experience, the accumulation of research on monkey Parkinson's disease models using the neurotoxin MPTP subcutaneously led me to believe that marmosets are not only an alternative to macaques such as cynomolgus monkeys, but are even more useful than them (Ando, ​​2018, Ando et al., 2020). However, in operant behavior research, which was the author's original field of expertise, the author has the impression that marmosets do not show as stable learning behavior as rhesus monkeys and rats. However, this is the case for learning behaviors such as food and juice reinforcement. For such learning, severe food or water deprivation treatment must be imposed in advance. Marmosets do not have a strong physical tolerance to such deprivation compared to rats and macaques. Therefore, the author believes that it is not easy to establish a strong and stable baseline behavior for food-reinforced or juice-reinforced operant behavior in marmosets that has been subjected to mild food or water deprivation in advance, as is the case for rats and macaques. If this operant behavior baseline is not stable, it is difficult to detect the behavioral pharmacological effects of drugs in a sensitive and objective quantitative manner. However, the author believes that this should be judged comprehensively and objectively after further research on operant behavior using marmosets has been accumulated.

On the other hand, marmosets respond sensitively to external sensory stimuli. It has been found that operant learning behavior can be established using this behavioral characteristic. In other words, we were able to establish an operant response to touching a tablet (iPad) screen in marmosets, with changes in audiovisual stimuli on iPad screen as the reinforcing stimulus (Ando et al., 2025). In this case, it was revealed that the reinforcing stimulus was not the food or juice that is usually used, but the changes on the iPad screen.

Next, the author would like to mention the possibility of using marmosets in the field of drug dependence studies, in which the author has been involved. The essence of drug dependence is psychic dependence, and in this regard, the self-administration method of drugs (intravenous/intragastric) in rhesus monkeys has been established as the most valid research method (see Drug Dependence Concept, Operant Behavior in Neuroscience ). It is extremely important to predict the presence or degree of psychic dependence potential of drugs in preclinical medical tests in the development of drugs that act on the central nervous system. Previously, the author conducted a pilot experiment in which a catheter was implanted in the vein of a marmoset. The aauthor observed that the marmoset actively self-administered cocaine, a typical psychic dependence producing drug, intravenously by lever pressing. If we could replace large macaques such as rhesus monkeys with marmosets to study psychic and physical dependence of drugs, we would be able to significantly reduce the facilities and costs required for drug dependence studies, and we believe that marmosets would greatly contribute to the progress of studies in this field. Here, we have only mentioned the possibility that marmosets can replace rhesus monkeys.

However, we do not believe that simply performing drug dependence tests currently performed on rats/mice (for example, the place preference test) on marmosets will create value in preclinical drug dependence evaluation simply because they are monkeys. Although the place preference test is an interesting subject from the perspective of behavioral pharmacology and conditioning, we believe that it is completed within the scope of experiments using rats/mice. If the place preference test in marmosets is to be used to evaluate drug dependence, a clear and concrete theory will be required as to what aspect of drug dependence this test is related to and what aspect of drug dependence it is detecting. There is already an established method for evaluating psychic drug dependence in animal experiments, the drug (intravenous/intragastric) self-administration method, and we believe that using marmosets in this method would be more meaningful and productive in drug dependence studies.

In addition, marmosets can be used in repeated-dose drug toxicity tests and reproductive and developmental toxicity tests in preclinical medical tests on drug safety. For the former, if marmosets can be used instead of repeated-dose toxicity tests of compounds in cynomolgus monkeys, etc., it will be advantageous in terms of resources, including facilities and test materials, and we believe that more accurate and useful test results can be obtained in terms of inter-individual homogeneity regarding data variability. In addition, reproductive toxicity tests have been detected in marmosets that cannot be detected in rats/mice (e.g., teratogenicity of thalidomide). There are probably many other areas where the usefulness of marmosets should be explored.

5. Summary

As mentioned above, marmosets have been shown to be useful in a wide range of fields, including neuroscience research, basic research into neuropsychiatric disorders, in vivo experimental medical research, and preclinical medical research, and future developments are expected. When marmosets are best matched with these research topics, new developments in that research field can be expected. However, the premise is that we must accurately determine the usefulness and limitations of this small monkey, which we believe is important.

6. References

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

Ando K, Inoue T, Hikishima K, Komaki Y, Kawai K, Inoue R, Nishime C, Nishinaka E, Urano K, Okano H (2020)  Measurement of baseline locomotion and other behavioral traits in a common marmoset model of Parkinson's disease established by a single administration regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: providing reference data for efficacious preclinical evaluations. Behav Pharmacol 31:45-60.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964884/pdf/bpharm-31-45.pdf

Ando K, Maeda J, Inaji M, Okauchi T, Obayashi S, Higuchi M, Suhara T, Tanioka Y  (2008)  Neurobehavioral protection by single dose l-deprenyl against MPTP-induced parkinsonism in common marmotsets. Psychopharmacology 195:509-516.

Fukuoka T, Nakano M, Kohda A, Okuno Y, Matsuo M (1997)  The Common Marmoset (Callithrix jacchus) as a Model for Neuroleptic-Induced Acute Dystonia. Pharmacol Biochem Behav: 58, 947-958.

Jenner P, Rose S, Nomoto M, Marsden CD (1987)  MPTP-induced parkinsonism in the common marmoset: behavioral and biochemical effects. Adv Neurol 45:183-186.

NIH 2019 Marmoset Community White Paper.　https://www.marmohub.org/white-papers

Servick K (2018)  U.S. labs clamor for marmosets.  Science 362:383-384.

Stephan H, Baron G, Schwerdtdfeger WK (1980)  The brain of the common marmoset (Callithrix jacchus) A Stereotaxic Atlas. Springer-Verlag, Berlin Heidelberg New York,

Following Articles in Japanese

Ando K (1918)  A common marmoset model of Parkinson's disease induced by administration of the neurotoxin MPTP – Preclinical evaluation using behavioral analysis – Obelisk Vol.23,1:14-22.

安東潔 (1918) 神経毒MPTP 投与によるコモンマーモセットのパーキンソン病モデル  

– 行動解析による前臨床評価を中心として – オベリスク Vol.23,1:14-22.　https://researchmap.jp/read0179769/published_papers/19447809

Tanioka Y   (1999)  Marmoset breeding, experimental techniques, and dissection, Ad Three.

谷岡功邦 (1999)  マーモセットの飼育繁殖・実験技術・解剖組織, アドスリー.

Nomura T,  Iinuma K  (1991)  From Six Mice, Kodansha.

野村達次・飯沼和正(1991) ６匹のマウスから, 講談社.

Nomura T,  Iinuma K  (2008)  Pioneering in vivo experimental medicine, Keio University Press.

野村達次・飯沼和正(2008)  イン・ビボ実験医学を拓く，慶應義塾大学出版会.

Nomoto M  (1995)  Application of marmosets (small monkeys) to pharmacological research. Japanese Journa of Pharmacology, 106:1, 11-18. Download PDF (6345K)

野元正弘 (1995)  マーモセット(小型のサル)の薬理学研究への応用. 日本薬理学雑誌106:1, 11-18.   PDFをダウンロード (6345K)