- Neuroscience research has for a long time not included female lab animals, which has skewed our understanding of how the brain works.
- Women are almost twice as likely to have bad reactions to drugs because trials have mostly used data from males.
- The idea that female lab animals are too hormonally variable has been proven wrong by science.
- Since 2016, the NIH has required that federally funded studies consider sex as a biological factor.
- If we don’t pay attention to sex differences in brain biology, it could make it harder to create good treatments for mental health issues.
For many years, the standard approach in neuroscience research has been to use male animals. Female lab animals were mostly left out because it was thought that their hormone cycles would confuse the data and make research too complicated. This long-term partiality has caused important gaps in what we know about the brain, actions, and how well drugs work in different sexes. As the field moves toward more practices that include everyone, it is becoming very obvious that studying both male and female organisms is not just more ethical; it is needed for strong, repeatable, and useful neuroscience.
A Long Legacy of Bias
The fact that female lab animals have been left out of neuroscience research is not by chance. It comes from past methods based on incorrect ideas. Researchers used to think that hormone changes related to the estrous cycle – the rodent version of the menstrual cycle – would make experiments harder by adding “noise” to the data. Because of this, they chose to make experiments simpler by only looking at males.
This easy way out in methods became a common practice. It was supported by the way research was usually done, limited money, and science education that highlighted models using only males. In many labs and studies, the idea became accepted that male data was not just enough but scientifically cleaner, more consistent, and therefore more wanted for forming general ideas.
However, making things simple should never be more important than being correct. Science gets better with complexity; it is the only way to really understand things. By picking what was easy over what was complete, researchers ignored half of the population in both animal models and when applying it to humans. This created biases that still impact medicine and mental health care now.
The Myth of Hormonal Variability
The thought that female animals are “too variable” to use in neuroscience experiments has strongly discouraged their use, but this is completely wrong. This false idea was disproven by a full review done by Beery and Zucker (2011). They looked at many traits across sexes in lab animals. Their study showed that females were not much more variable than males. In fact, in many situations, males were more variable.
For example, male rodents can show a lot of variability because of things like fighting, marking territory, and social rank. These things affect stress, hormone amounts, and finally, what happens in experiments. Also, the estrous cycle in female rodents is now understood better. It can be tracked accurately and taken into account in experiment plans.
Even with this strong proof, the “high variability” false idea still exists in some parts of the science world. It continues to affect decisions about money, articles reviewed by other scientists, and even how labs work inside. To deal with this lasting partiality, we need better teaching and awareness, especially when training young scientists. This should be combined with clear rules from institutions that back methods that include everyone.
Consequences of Exclusion
Not including female lab animals does not just reduce data; it makes it possibly wrong. When we only study one sex, we get an unfinished picture of how the brain works and its functions. This can cause us to make wrong guesses about how everyone reacts to things that cause reactions, medicines, or sickness.
For example, basic studies about learning, memory, and stress often only used male animal models. From these studies, we made ideas about behavior and reactions to mental health drugs that may not be true for females. Research shows that female brains can react differently to the same things that cause reactions, like fear, stress, and pain. This shows why it is needed to analyze sexes separately.
These missing pieces of knowledge have effects later on. Treatments made and tested only on males might not work or even be bad for females. Even worse, these treatments can hide the signs in women, which can cause wrong diagnoses or treatment delays. The problem with not paying attention to sex differences is not just about school knowledge; it affects clinics and society.
Real-World Impact: Disparities in Drug Response and Diagnosis
The actual effects of leaving out female animals from neuroscience research are very noticeable. Women are 1.5 to 2 times more likely than men to have bad reactions to drugs, according to a study in 2012 by Regitz-Zagrosek. This is because drug information, from how molecules work together to how much medicine to give, has usually come from studies that focused on males.
This difference affects many health problems, from feeling down and worried to heart problems and brain disorders. In the past, even tests on people did not include enough women, which made the problem worse that started in the early stages of testing on animals.
Mental health is a very pressing area. Problems like feeling down and anxiety affect women more often, but much of what we understand about them comes from models that favored males. For example, PTSD shows itself differently in sexes: men might be more watchful, while women might be more likely to disconnect from reality or feel stress inside. These small differences are not just interesting for study; they directly change how diagnoses are made and how treatments are done.
Sex Differences in Brain Biology
New progress in neuroscience has shown that male and female brains are different in both small and big ways. Even though saying “male brain versus female brain” makes complex brain traits too simple, sex does have an effect on how some parts of the brain are built and how they talk to each other.
For example, pictures of the brain and animal studies show that males and females can use different brain circuits to do the same thinking jobs. One study by Gruene et al. (2015) looked at how rodents process fear. It found that male and female brains used different paths between the front part of the brain and the amygdala when learning to connect things with danger. These differences were not just on the surface; they were deeply set in how the brain is built and works.
These kinds of findings are very important for treatments for mood and worry problems, which start in these same brain circuits. If we don’t understand these sex-based patterns, researchers and doctors might mistake normal differences for problems or, even worse, give the wrong treatments completely.
Case Study: Differences in Fear Processing
How fear works in the brain is a very good example of why sex differences are important. Fear is not just a feeling; it is a built-in way to survive that is deeply connected to specific parts of the brain, including the amygdala, hippocampus, and prefrontal cortex.
Research by Gruene et al. (2015) showed that male and female rats use different brain paths to deal with learned fear. In males, one path is used more, while in females, a different brain path becomes active. These results strongly suggest that treatments to lessen fear, like exposure therapy, might work better for one sex than the other, depending on how they are made.
This does not mean making completely different treatments, but instead creating adjustable treatments that can be changed for each person based on brain traits linked to sex. Adding these understandings to treatment planning could greatly improve results for people dealing with long-term stress, PTSD, or fear-related problems.
Progress and Inclusion Mandates
Because of the obvious sex partiality in biomedical science, the NIH took action. Starting in January 2016, any research funded by the NIH that involves vertebrate animals or humans must consider sex as a biological factor (SABV). This rule says that scientists must explain why they are including or leaving out either sex and to plan their experiments to study sex-based changes when it makes sense.
This action is a big move ahead in fixing past mistakes. It pushes those who check grant applications and researchers to think carefully about how widely their data can be used. It also starts a spread of changes throughout universities, changing how experiments are planned, done, and judged.
However, rules are only as good as how well they are put into practice. Following the rules has been inconsistent, partly because some scientists don’t want to change old habits. Some scientists are concerned that including both sexes makes the sample size twice as big and analysis more complex, using up limited money and time.
But these worries are not as important as the problems caused by science that is wrong or not complete. Better tools, free statistical programs, and set ways of doing things are now available to help labs meet SABV rules without too much trouble.
Inclusive Research Breeds Discovery
Different from the worry that using female animals would cause too much confusion in data, including both sexes has really shown scientific truths that were hidden before. One example is about cannabinoids: research found that female rats acted and reacted to chemicals in the brain differently to cannabinoid exposure based on what part of their estrous cycle they were in.
These findings are not unusual; they suggest biological ways that could better treatments for long-lasting pain, mood problems, or how we control appetite. The only reason these were not found out for so long is because studies did not use females in the beginning.
By using female lab animals, scientists are not adding “noise” to research; they are adding needed parts that make the whole thing complete.
Understanding Female Brain Development
Puberty is a very important time for brain growth, and it is a time with clear sex differences. Female lab animals show different paths of brain growth during teenage years compared to males. This affects many things, from how well they remember things to how easily they get stressed and their social behaviors.
These growth differences are not just small details; they can be the start of problems like worry, feeling down, and ADHD. These often start in teenage years and affect girls differently than boys. By studying female lab animals through different stages of growth, researchers can plan better systems to find these problems early and ways to prevent them.
Understanding how female brains grow as it happens gives a scientific advantage in reducing mental health differences that start in teenage years and often get bigger as adults.
Challenges in Implementation
It is true that adding sex-based analyses does create practical problems. Researchers have to make their sample sizes twice as big, create ways to watch estrous cycles, and sometimes make two sets of statistical models. For labs with few resources, this can be a real problem.
However, these problems can be overcome. Computer systems now help with tracking hormone cycles, and statistical programs can easily study how different factors affect each other. Journals and groups that give money can offer rewards and help to make it easier to move toward protocols that include everyone.
What is harder to see, but even more difficult, is the change in thinking needed. Many generations of scientists have been taught in a system that put male models first. To change this history, it takes not just new science training but a culture shift in universities. This starts with updated teaching plans, active guidance, and making institutions responsible for research practices that include everyone.
Beyond the Binary: A Look at Gender-Inclusive Neuroscience
Talking about sex differences is going past just male and female. As our understanding of sex and gender changes, neuroscience also needs to change. Brain structures and functions are affected not just by chromosomes but by many other things, such as hormone amounts, stress from the surroundings, and gender identity.
Transgender and non-binary people often have hormone treatment that changes brain chemicals and structure in ways that science is just starting to understand. Neuroscience that includes everyone must now grow to include checking hormone levels, differences in identity, and more detailed studies that show the real experiences of different groups of people.
Tools like machine learning, fMRI, and blood hormone tests can help researchers start to map out how identities based on a spectrum affect thinking, feeling, and how the brain changes.
The Road Ahead: Building a More Equitable Neuroscience
The future looks like it will have strong tools that make neuroscience that includes everyone not just doable but more productive. Machine learning programs can find small patterns in data related to sex, while single-cell sequencing shows how male and female brain cells show genes differently even in the same situations.
Going ahead, researchers need to ask better questions, not just easier ones. The NIH’s rule has shown the way, but real change needs teamwork. Journal editors, grant groups, and institutional review boards all have a part to play in making inclusion a normal thing, not something special.
Neuroscience needs to be fair not just in what it studies but in how it is set up. It should give equal chances for all opinions and all sets of data to help create the next part.
Why This Matters for Mental Health and Society
When female lab animals are left out, so are the answers to important mental health questions that affect millions of women and girls. Not studying female biology leads to a single approach for everyone in both finding and treating problems, which does not correctly represent the people it is trying to help.
A more even approach to neuroscience can guide the way in planning better, more customized treatments for everything from autism spectrum problems to schizophrenia to drug use problems. Public health needs this inclusion not just because it is good, but because it is required.
We all should have medicine based on facts that are true for everyone, not just for those who are easiest to study.
A More Inclusive Mind
Using female lab animals in neuroscience is not just a small ethical point; it is a scientific must. Understanding sex differences in how the brain works makes research stronger, not weaker. It makes medicine safer, more correct, and able to be used more widely. Now is the time to take action because brains are not all the same, and science should not be either.
