Guidelines for Animal Experimentation in Neuroscience

September 25, 2015
Japan Neuroscience Society (JNS)

PREAMBLE

  1. Objectives
    These guidelines are intended to assist JNS members to understand the significance of, and legitimately implement, legally compliant animal studies.
  2. Social Significance of Neuroscience Research and the Need for Animal Studies
    1) Social Significance of Neuroscience Research
     The goal of neuroscientific research is to increase understanding of the structure and function of the brain and nervous system. Clarification of the pathogenesis and pathophysiology of diseases and disorders affecting the brain and nervous system can help improve their diagnosis, prevention, and treatment. Currently, there are many health challenges that are related to disorders of the cerebral and nervous system, such as dementia associated with aging, depression, schizophrenia, and other psychiatric diseases, and autism spectrum disorders and other developmental disabilities. These problems require urgent solutions. In addition, new therapeutic methods need to be developed to treat intractable disorders and conditions of the nervous system, such as spinal injury and so-called “incurable” neurological diseases. Moreover, the elucidation of the information processing mechanism of the brain is expected to provide a basis for the development of the brain-machine interface and humanoid robots. Neuroscience research has significantly contributed to society with many important achievements. However, much still remains to be explored, and continued basic research on the structure and function of the cerebral and nervous system will be required to contribute to human well-being and development.

    2) Need for Animal Studies
     The complexity of the brain and nervous system is the result of the organic network of nerve cells, which contain a large variety of functional molecules. The system regulates not only daily cognitive functions, such as perception, memory, reasoning, judgment, and decision-making, but also emotional, spiritual, and psychological activities. Thus, in order to understand the neurological system, neuroscientists need to isolate the biological components constituting the brain and to thoroughly investigate their morphology and activity. Neuroscientists also need to investigate the collective dynamics of the brain, which functions by coordinating a variety of complex neural circuits. For this purpose, it is necessary to explore how a live brain actually works in vivo. Human studies should principally rely on noninvasive approaches for ethical reasons, and neuroscientists are generally not allowed to investigate the organ, tissue, or cell activities in vivo using invasive methods. These ethical considerations underscore the importance of animal studies in neuroscientific research as mentioned above. Animal studies are a mainstay for scientific and medical advances related to the human brain, and their use will allow for assessment of the safety and benefits of new diagnostic and therapeutic modalities.

  3. Legitimate Implementation of Legally Compliant Animal Studies
     In Japan, animal studies are regulated by The Act on Welfare and Management of Animals (hereafter referred to as the “Animal Welfare Act”) and The Standards Relating to the Care and Management of Laboratory Animals and Relief of Pain (hereinafter referred to as the “Standards”) [1, 2, 12, 13]. The Animal Welfare Act has stipulated the principles of the “3Rs” of replacement, reduction, and refinement. Replacement refers to proactively adopting methods which avoid or replace the use of animals, reduction relates to effective methods that reduce the number of animals being used, and refinement refers to efforts to improve animal care and experimental procedures to minimize study-related pain and distress out of respect for the life of experimental animals. Under the principles of 3Rs, the Standards have stated that, since animal experiments are “indispensable for advancing life sciences and developing medical technologies,” laboratory animals “shall be appropriately cared for, managed, and used for scientific purposes with due appreciation of and responsibility for their role.”

     Based on the Animal Welfare Act and the Standards, the Ministry of Education, Culture, Sports, Science and Technology (MEXT), the Ministry of Health, Labour and Welfare (MHLW), and the Ministry of Agriculture, Forestry and Fisheries (MAFF) have issued their guidelines on experimental animal welfare (hereafter referred to as the “Guidelines”): Basic Guidelines on Animal Experiments etc. in Research Institutions, etc. (MEXT, [3]), Basic Guidelines on Animal Experiments etc. by the Ministry of Health, Labour and Welfare (MHLW, [4]), and Basic Guidelines on Animal Experiments etc. in Research Institutions etc. Supervised by the Ministry of Agriculture, Forestry and Fisheries (MAFF, [5]).

     In accordance with the Animal Welfare Act, Standards, the Guidelines issued by relevant regulatory authorities, and the Science Council of Japan’s Guidelines for Proper Conduct of Animal Experiments [6], each research institution is required to properly carry out animal studies under the supervision of the institution’s head based on specific in-house rules and regulations for animal experimentation and related matters. All animal experiments must be appropriately implemented according to the above-mentioned legal and technical documents. Depending on the type of laboratory animals and experiments, researchers must conform to the legal requirements provided in: the Act on the Conservation of Biological Diversity Through Regulations on the Use etc. of Genetically Modified Organisms etc. [7]; the Act on the Prevention of Damage to the Ecosystem etc. by Specified Alien Species [8]; and the Details on the Methods for Care and Management of Specified Animals etc. (public notice issued by the Ministry of the Environment) [9].

MAIN TEXT

  1. Animal Experiments Conducted at Research Institutions
     Research institutions must perform animal studies appropriately based on the relevant established Guidelines, as outlined below.
     At research institutions conducting animal experiments, the head of the institute assumes the ultimate responsibility for the program. Under the leadership of the head, in-house rules and regulations are established, including the formation of the Institutional Animal Care and Use Committee [IACUC]. The researcher planning an animal study must submit the study protocol to the IACUC for review and approval before he or she can start the study. Research staff members engaged in animal experimentation must be adequately trained.
     In order to ensure transparency, the institutional management system should regularly be assessed not only by self-inspection and review but also by external third-party auditing programs. The results of the assessment must be disclosed through appropriate channels.
  2. Animal Experimentation
    1) Removal and Alleviation of Pain and Distress
     The investigator must make maximum efforts to avoid causing pain and distress to experimental animals.
     When performing surgical treatment, the experimenter must ensure appropriate preoperative management, sterilization, disinfection, and infection control. Pain must be minimized by medication and anesthesia pre- and intraoperatively and by medication and nursing care postoperatively. Animals to be placed in restraint devices must be sufficiently trained to adapt to the equipment. When restricting access to food and water, the investigator must monitor the health status of the animal subjects so as to avoid distress. Particular attention must be paid to the use of anesthesia to alleviate discomfort.

    2) Creation and Retention of Animal Documentation
     It is the duty of the investigator and the research institution to create and retain animal documentation that records the progress of the study. These files must contain the approved version of the study protocol and documentation of the actions taken to address health problems and accidents, study results, and the arrangements for publishing them.

    3) Post-Study Treatment
     When sacrificing experimental animals following completion of the study, the investigator must perform euthanasia to ensure animal welfare. Euthanasia should induce an immediate loss of consciousness and death without causing pain or distress. Euthanasia is typically performed by administering excessive anesthetic doses, as recommended in the Guidelines for Methods of Killing Animals [10].

  3. Procurement and Transfer of Animals
     All experimental animals must be obtained lawfully. If wild animals are to be used for experimentation, they must be procured through legitimate means that do not interfere with wildlife conservation. In the case of importing animals, attention must be paid to comply with the Washington Convention on International Trade in Endangered Species of Wild Fauna and Flora. Before new animals are accepted into the laboratory, they must be quarantined by the veterinarian or other personnel with appropriate expertise to prevent contagion among the experimenters, animal technicians, and residential animals. Careful testing is required to prevent zoonotic infection among others.
  4. Animal Care and Management
    1) Evidence-Based Husbandry
     Experimental animals must be cared for and managed based on knowledge, skills, and expertise in veterinary science and experimental zoology. From the view point of animal welfare, animal management ranges from physical to behavioral and emotional health [11]. Research institutions conducting animal experiments must create an animal husbandry manual.

    2) Health and Safety of the Experimenter and Animal Technician
     Each research institution must provide the animal technician and investigator with a safe and healthy working environment where they can fulfill their tasks of animal husbandry and experimentation. Efforts must be made to avoid animal bites and infection as well as zoonotic infection.

    3) Buildings and Facilities
     As a general rule, animals should be housed in a clean and controlled laboratory environment. In cases where the research institution must keep the animals outside the laboratory, careful management strategies must be in place to prevent escape and theft of the animals and to prevent noise, smell, and other unpleasant environmental stimuli and infection. It is recommended that the staff area and the animal area be separated to achieve quality animal care and a healthy and comfortable working environment for the staff.

    4) Rearing Environment and Husbandry Practice
     To allow for a comfortable living environment, cages must be large enough and suitable for the species and size of the animals to house. Cages and their surrounding areas must be kept clean, well-ventilated, and controlled for illumination, temperature, and humidity. Chow must reflect the food preferences of the animals and must be nutritionally appropriate. Access to fresh potable water must be granted. In addition, to reduce the anxiety and stress of the housed animals, they must be allowed to perform physical activities and movements that are natural to them.

    5) Disease Control
     The health status of the animals must be checked periodically, and species-specific disease control measures must be implemented. In the case of sick animals, appropriate actions must be taken immediately in consultation with a veterinarian and other experts to prevent the spread of the disease.

  5. JNS Animal Experiment Committee
     The JNS Animal Experiment Committee will monitor the latest developments in animal experimentation in Japan and overseas and will disseminate relevant information to the JNS members. The Animal Experiment Committee will provide guidance and support upon request from research institutions.