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3R-INFO-BULLETIN 6 - September 1995

Call for 3R-Research Proposals

Programme and Funding

The Swiss FOUNDATION RESEARCH 3R promotes research to reduce, replace and refine the use of animals in biomedical tests. In this context, «refine» means the minimization of animal discomfort, stress and pain when alternative, animal-free testing is not feasible.

A total of SFr. 900'000.- are presently available.
The Foundation is confident that it will be possible to continue funding at this level in the future. Research grants are issued on a competitive basis with preference given to projects promising applicability in the near future.

Funding Priorities

The priorities include new testing models for:

The Foundation selected these particular animal models as priorities for the following reasons:

  • these animal models are used in routine testing
  • comprehensive, validated in vitro alternatives are not yet available
  • these experimental procedures involve a considerable amount of stress, pain or discomfort
  • ethical considerations using these animal models.

From the human point of view, biomedical research in these areas is vital in order to further our understanding of the pathophysiology of these life-threatening infections and debilitating diseases. Better understanding will lead to better treatment, saving lives and improving the quality of life for afflicted individuals. Research proposals promoting the goals of 3R in these areas are welcomed.

Therapy of Arthritis

Animals have long been used to study the etiology, pathology, mechanism, and therapy of arthritis. Among the most commonly used animal models of arthritis are the subcutaneous air pouch model, antigen-induced models (adjuvant, collagen, or bacterial antigens injected into the footpad or tail), and animal strains that spontaneously develop arthritis. All the models entail side effects causing acute and chronic pain in the animal alongside the primary symptoms of arthritis (synovitis, degradation of bone and cartilage, other chondropathic effects and tissue damage in the animal's joints).

The various methods of inducing arthritis (chemically or surgically) give rise to different types of arthritis (mono-, poly-, or systemic arthritis). From the point of view of animal welfare, all these models have drawbacks, because they involve unavoidable, chronic pain for the test animals.

Anticonvulsive Therapy

About 1% of our population suffers from various forms of epilepsies, but present therapy options for juvenile and adult epilepsies are less than ideal. Tolerance to some drugs (e.g. benzodiazepines) develops rapidly, side-effects of anticonvulsant therapy may be disturbing, and many patients respond only partially to therapy. There is an urgent need to develop new drugs.

To date, the anticonvulsant potential of new drugs is characterized in a first step in vitro and in a second step always in vivo. At present over 50 animal models are available. Seizures that phenomenologically resemble convulsions in humans are elicited in animals (mostly rats or mice) either physically, by maximal electroshock or auditory stimulation, or chemically. Currently, the maximal electroshock seizure (MES) and the pentylentetrazol (PTZ) tests are the most widely used models. Seizure models are also used in toxicological testing, to rule out unwanted proconvulsant or epileptogenic side-effects of other, unrelated drugs.

Mainly for such purposes, i.e., to determine proconvulsant drug effects, agents are administered at subconvulsant doses. This kind of treatment may lead to incomplete convulsion (with only partial loss of consciousness). In addition, when agents are administered at convulsive doses the animals not sacrificed following the convulsion regain consciousness after the convulsive event within minutes. Such situations are accompanied by a high degree of stress and discomfort for the animal.

Antimicrobial Prophylaxis and Therapy

Registration and regulatory authorities require antimicrobial agents to be tested routinely in animal challenge models. Many animals are needed to test the protective activity of drugs against infectious diseases (e. g. pneumonia by pneumococcus, encephalomyocarditis, malaria).

Therapy of Septic Shock

Septic shock is a major cause of death in patients in intensive care units. The protective activity of substances against septic shock is tested initially in a pharmacological animal model.

Septic shock is induced in experimental animals e.g. by the application of endotoxin. This leads to multiple organ failure in the animals, a sequence of events which is obviously very stressful: in preclinical animal tests, survival of the animals is scored as therapeutic «success». Animals are also used in research on reducing pain in septic shock victims.