How Animal Models Paved the Way for Innovation in Neuroscience

Introduction

What can we learn from teaching rats how to drive cars? More than you might think. Researchers at the University of Richmond discovered that animals trained to drive exhibited greater emotional resilience. This finding has provided valuable insights into neuroplasticity—the brain’s ability to adapt [1]. In many cases, animal research serves as the foundation for groundbreaking discoveries in neuroscience. Nearly every prescription medication on the market has been developed with insights from animal models. These models allow researchers to explore concepts and use techniques that would not have been permissible in human subjects, making them crucial to advancements in human well-being. 

History of Animal Research Regulations

As early as the third century BCE, physicians utilized animals for investigative surgeries, contributing to our foundational understanding of how animal physiology can be mapped to that of humans. In 1876, the United Kingdom passed the first legislation regulating these experiments—the Cruelty to Animals Act which prohibited researchers from inflicting pain on animals unless deemed necessary for scientific advancement [2]. Similar regulations have since emerged, including the Laboratory Animal Welfare Act (AWA) of 1966, which set standards for appropriate animal care. An amendment to the AWA introduced the requirement that modern-day animal research proposals be reviewed and approved by an Institutional Animal Care and Use Committee (IACUC), which includes at least one veterinarian, one scientist, and one non-affiliated member to ensure ethical considerations are addressed [1]. 

Discoveries: Drug Development

Animal models have been crucial in facilitating numerous discoveries including novel treatments for psychiatric disorders [3]. In 2023 the World Health Organization estimated that 5% of adults suffer from depression, a condition that can be life-threatening if left untreated [4]. Antidepressant medications, such as Lexapro® and Prozac®, can create clinically significant improvements in mood and functioning [5,6]. Animal research has been the backbone of drug discovery and development for widely used drugs including antidepressants [7,8], antipsychotics [9] and anti-anxiety medications [10]. Since new treatments are typically tested in animals before progressing to human trials, this research plays a crucial role in evaluating safety and efficacy.

Discoveries: Significance of Dopamine 

Neurotransmitters are chemical messengers that deliver signals throughout the body [11]. Dopamine, a neurotransmitter important in learning, voluntary movement, and the brain’s reward system, has also been found to be clinically relevant for disorders such as Parkinson's disease (PD) [12]. In 2000, Arvid Carlsson won a Nobel Prize for his groundbreaking discovery of dopamine in the 1950s using a rabbit model. Carlsson’s use of rabbits demonstrated the efficacy of the drug levodopa in counteracting a loss of motor control seen in PD. Levodopa is still the primary treatment used today to slow the progression of PD, a treatment that wouldn’t be available without animal models [13]. 

Strengths 

Animal research has allowed for discoveries in neuroscience to be made that would not have been achievable in humans alone. It provides us with the ability to test drug efficacy, simulate human diseases, and explore the neurobiology of behavior [14]. Many of the potentially life-saving treatments for common disorders, such as major depressive disorder and PD, have been facilitated through animal model research [3, 15]. Animal models also allow for the control of extraneous variables like diet, exercise, disease, and socioeconomic status that are difficult or impossible to control for in human studies [16].

Challenges 

While the benefits of animal research are evident, so are the ethical concerns. Research involving animals remains a sensitive, complex, and polarizing topic, raising important moral questions [17,18]. A recent poll found only 47% of Americans support using animals in research [19]. Mice are the most common laboratory animals with rats and mice comprising 95% of animals used in biomedical science [20]. There are differences in mouse and human genetics, coding regions for proteins are approximately 15% dissimilar [21]. These contribute to issues in translation, the process in which we use laboratory findings to improve human health.

Beyond “Lab Rats”

Although rodents dominate animal research, many other species are also frequently studied and have contributed significantly to our knowledge of human illness and physiology [20]. We discovered “biological clocks” in fruit flies [22], Zebrafish have advanced cancer research [23], shrews inform our understanding of nausea [24] and non-human primates remain excellent models for translational neuroscience research [25]. 

The Future of Animal Research

An estimated 79.9 million animals are currently used in research each year [26, 27]. There is a growing movement to develop alternatives to animal models. Emerging alternatives like artificial intelligence models, 3D tissue cultures, and stem cell research aim to reduce animal use while improving the relevance of findings to human diseases [28, 29, 30]. As technology advances, alternative methods may reduce the need for animal research while improving the safety and effectiveness of treatments for humans. That being said, animal research remains as vital to scientific progress today as it has historically.

References

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