Nutrition and Drugs

Effect of Fish Oil on Mouse Behavior

By February 28, 2018 No Comments

Fish oil is one of those things that is constantly being emphasized as something you need more of. But, why? Thanks to animal models, it has become easier for scientists to study and understand the effects and benefits of fish oil. Fish oil powerfully impacts both the biology and behavior of lab specimens in many more ways than just one.

Understanding Fish Oil

Fish oil is a supplement that serves to enhance cognitive abilities and ward off dangerous health conditions. Fish oil’s constituents include:

  • Eicosapentaenoic acid (EPA)
  • Docosahexaenoic acid (DHA) [1]

Fish oil is classified as a polyunsaturated fatty acid, often referred to as an omega-3 or n-3 polyunsaturated fatty acid (n-3 PUFA). Sometimes the greek letter ω for ‘omega’ is used as a symbolic abbreviation. So, omega-3 can be written as ω3.

Omega refers to the chemical structure of the fatty acid chain itself. Each fatty acid chain has a beginning and an end. Its beginning is referred to as the “alpha” while the end is referred to as the “omega.”

Now, here comes the fascinating part. The dash in omega-3 is actually a minus sign, not a dash, which reveals something about its nature. A main feature of the chemical structure in PUFAs is their long carbon chain. Omega-3’s have a double bond on the 3rd carbon from the bottom end, hence the -3. In a different fatty acid, such as omega-6, the double bond would be on the 6th carbon from the omega end.

effect of fish oil on mouse behavior Omega--3-and-Omega--6

Benefits of Fish Oil

Fish Oil Decreases Inflammation and Affects Molecular Markers.

Mice that are deficient in omega-3 exhibit memory deficits as well as poor hippocampal plasticity.

Also, a lack of omega-3 is associated with inflammation. Inflammation is very detrimental because it can negatively affect both cognition and behavior [2][3].

Meanwhile, the presence of n-3 PUFA is associated with:

  • Modulating oxidative stress
  • Neurogenesis
  • Altered intracellular signaling
  • Modulating neuroinflammation
  • An impact on gene expression[1].
  • Improved synaptogenisis
  • Stronger learning abilities
  • Powerful executive functions

Fish Oil Affects Aging Mice

In a recent experiment by Cutuli et al., the positive effects of fish oils were demonstrated in aging mice [5]. The researchers sought out to show that giving mice n-3 PUFA would lead to both measurable changes in behavior as well as differences in gray matter in the brain.

For the experiments, male aged C57B6/J mice were given an n-3 PUFA supplement for 8 weeks, but data collection began at the 5-week mark [5]. To test the physical effects of n-3 PUFA on the brain, as well as the emotional and cognitive functions, the researchers used an assay of techniques. The following tests and chambers were employed:

  • The Light/Dark test was used to measure levels of anxiety and exploration in mouse.
  • The Y-maze with objects was used to determine novel object recognition memory by comparing the time that the mice spent in contact with novel objects versus familiar objects.
  • The Morris Water Maze was used to assess mice ability to localize. The mice were expected to localize a hidden platform after being exposed to it briefly. Behavior was measured by categorizing their swimming trajectories.
  • Sociability and Memory test was used to measure both social motivation and social novelty. This test was used because aging is associated with impairments in social memory. To measure these outcomes, discrimination indexes are calculated based on exhibited behavior.
  • Elevated Plus Maze was used to test the levels of anxiety in the mice.
  • The Porsolt test, otherwise known as the behavioral despair test, is an apparatus composed of a tall cylinder filled with water wherein a mouse can be placed and their reaction measured in terms of active or passive behaviors.

These tests served as the basis of gathering a wide array of data describing the behavior of aging mice.

To get a closer look at the brain, the mice were sacrificed and biochemical analyses, as well as voxel-based morphometry (VBM), were performed. VBM revealed that the aged mice on n-3 PUFA supplements had significantly larger gray matter value in:

  • The posterior hippocampus
  • The medial prefrontal cortices
  • The retrosplenial cortices

In order, to establish a relationship between the behaviors and the gray matter volume, the researchers used the gray matter maps to create a voxel-wise regression of the individual behavioral scores.

The aging mice given n-3 PUFA supplements had improved mnesic functions. This group

effect of fish oil on mouse behavior

performed better in the Y-maze, meaning their novelty recognition abilities had a better discrimination index.

While in the Morris Water Maze, the n-3 PUFA mice had higher retention for the platform’s location than the control group did. The aging n-3 PUFA mice also showed better social memory. Their social memory index was higher than that of the control’s.

Also, the aging mice given n-3 PUFA supplements performed better on the Porsolt test and had more active behaviors than control mice. Using the Elevated Maze Plus test and the Dark/Light test, it was established that the two groups did not differ in their exhibited anxiety levels.

To measure the effect of n-3 PUFA on cell membranes, they took the concentrations of DHA and EPA, in order to further explore any possible influences on neuroinflammation and cognitive impairment. The aged mice taking an n-3 PUFA supplement had higher levels of DHA and EPA in the

  • Hippocampal regions
  • Prefrontal regions
  • Retrosplenial regions
  • Orbitofrontal areas

By demonstrating the correlation between larger brain volume in specific areas as well as better behavioral, cognitive, and emotional scores, the researchers demonstrated that n-3 PUFA supplements were able to counteract the deficits associated with aging-related decline while having both a structural and functional effect.

Translational Research

Fish oils have gained a rep for many significant and important things, from creating a buffer against inflammation to alleviating depressive symptoms.

Human studies have consistently demonstrated that fish oils have a strong effect on decreasing triglycerides by 15-30% [6].

Fish oils have a strong effect on decreasing depressive symptoms. In people that are really depressed, fish oil has effects comparable to those of fluoxetine and other pharmaceutical drugs [7].

Furthermore, children that are diagnosed with ADHD have demonstrated a minor decrease in their symptoms after taking more than 300mg of DHA supplements [8].

Also, many researchers are exploring the effects of fish oil on a variety of neuropsychiatric and neurodegenerative conditions, from attention deficit hyperactivity disorder (ADHD) to Huntington’s disease to depression [10].

Effect of Confounding Variables

There is much to be researched when it comes to fish oils. Two major areas of concern include investigating the effect of confounding variables and gaining a deeper understanding of the molecular mechanisms involved.

Future studies need to address the confounding factors which the previous studies have failed to do. Confounding variables of interest include:

  • genetic background
  • lifestyle choices (such as sleep, vitamin supplements, exercise)
  • socio-economic status

All these factors need to be controlled for, in order to isolate the exact effects of omega-3 and further understand its neuroprotective nature [5].


Fish oils are a powerful dietary supplement with definite effects on the nervous system. Though the precise nature and extent of these effects are still being studied, their positive impact is worth taking advantage of.

Fish oils have been demonstrated as deterring cognitive deficits associated with age, affecting the symptoms of many clinical populations (from depression to ADHD) for the better, and being overall promoters of health.

In order to get a closer look at just how fish oils perform their magic and under what circumstances these advantages emerge, animal models are being employed by researchers to take science to the next level.


  1. Venna, Venugopal Reddy, et al. “PUFA induce antidepressant-like effects in parallel to structural and molecular changes in the hippocampus.” Psychoneuroendocrinology 34.2 (2009): 199-211.
  2. Irwin, Michael R. “Inflammation at the intersection of behavior and somatic symptoms.” The Psychiatric clinics of North America 34.3 (2011).
  3. Dantzer, Robert, et al. “From inflammation to sickness and depression: when the immune system subjugates the brain.” Nature reviews. Neuroscience 9.1 (2008): 46.
  4. Simopoulos, Artemis P. “The importance of the ratio of omega-6/omega-3 essential fatty acids.” Biomedicine & pharmacotherapy56.8 (2002): 365-379.
  5. Cutuli, Debora, et al. “Effects of omega-3 fatty acid supplementation on cognitive functions and neural substrates: a voxel-based morphometry study in aged mice.” Frontiers in aging neuroscience 8 (2016).
  6. Boberg, M., et al. “Supplementation with n‐3 fatty acids reduces triglycerides but increases PAI‐1 in non‐insulin‐dependent diabetes mellitus.” European journal of clinical investigation 22.10 (1992): 645-650.
  7. Peet, Malcolm, and David F. Horrobin. “A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs.” Archives of general psychiatry 59.10 (2002): 913-919.
  8. Gustafsson, Per A., et al. “EPA supplementation improves teacher‐rated behaviour and oppositional symptoms in children with ADHD.” Acta paediatrica 99.10 (2010): 1540-1549.
  9. Kiecolt-Glaser, Janice K., et al. “Omega-3 supplementation lowers inflammation in healthy middle-aged and older adults: a randomized controlled trial.” Brain, behavior, and immunity 26.6 (2012): 988-995.
  10. Bozzatello, Paola, et al. “Supplementation with omega-3 fatty acids in psychiatric disorders: a review of literature data.” Journal of clinical medicine 5.8 (2016): 67.

About Ana Zdravic

Ana Zdravic earned her BSc in Psychology from the University of Houston while minoring in creative writing. She is currently in Europe pursuing her master's degree in cognitive science and is thinking about going for a doctorate. Her research interests include stress, nutrition, exercise, creativity, and quality of life.