Will Rats Also Suffer From Depression This Winter?
Dec 10, 2024
By 
Tanel Petelot

It may sound absurd, but research in mental health often begins with rats. Before testing an innovative treatment on humans, it must first undergo rigorous preclinical phases, where animal models are used to simulate disorders like depression and anxiety. Yes, we can induce "depression" in rats. Why? To better understand the mechanisms of these disorders and evaluate the efficacy of treatments.

How Do You "Depress" a Rat? 🐀

Researchers have developed standardized methods to induce depression-like behaviors in animals. These models are crucial for exploring the biological causes of depression and testing new treatments before moving to human clinical trials. Here are some common methods:

1. Chronic Mild Stress (CMS)

In this model, rats are exposed to various unpredictable stressors (e.g., light cycle changes, social isolation, or food restriction) over several weeks. This method replicates symptoms similar to human depression, such as anhedonia (loss of pleasure). A decrease in the consumption of sweetened water, typically highly appealing to rats, is often used as an indicator of this symptom.

2. Reserpine-Induced Depression

Reserpine, a drug that depletes monoamines like serotonin and dopamine, is administered to induce depressive behaviors. Animals become lethargic, less responsive, and show signs of apathy. This model is particularly useful for testing drugs targeting neurotransmitter pathways.

3. Genetic Models

Some animals are genetically modified to exhibit increased vulnerability to stress or specific traits associated with depression. For example, mice lacking the serotonin transporter gene exhibit heightened anxiety and depressive behaviors, reflecting the importance of this pathway in mood disorders.

4. Learned Helplessness Model

This model mimics feelings of helplessness observed in human depression. Animals are subjected to situations where they cannot escape stress, such as unavoidable mild shocks. Later, even when escape becomes possible, they no longer try—a behavior interpreted as learned helplessness.

Concrete Examples: Cybin and Lykos Therapeutics

Cybin: From Animal Models to Clinical Success

Cybin, a major player in psychedelic therapy development, has conducted extensive preclinical studies for compounds like CYB003. These studies utilized animal models to explore:

  • Pharmacodynamics and Pharmacokinetics: Comparing CYB003’s effects to those of natural psilocybin.
  • Therapeutic Efficacy: Likely employing models such as stress- or reserpine-induced depression to observe key behaviors like anhedonia and helplessness.

The findings demonstrated that CYB003 offers improved bioavailability and fewer side effects compared to traditional psilocybin, paving the way for successful human trials where it showed remarkable remission and response rates for major depression.

Learn more about Cybin's CYB003 data.

Lykos Therapeutics: MDMA and Resilience to Stress

Lykos Therapeutics focuses on MDMA-based therapies, particularly for post-traumatic stress disorder (PTSD). Their preclinical work included:

  • Animal Models of PTSD: Simulating trauma exposure to evaluate MDMA’s effects on emotional regulation.
  • Social Behavior Assessments: Demonstrating that MDMA fosters prosocial behavior, critical for therapies targeting empathy and emotional resilience.

While their findings showed promise, Lykos encountered regulatory hurdles in human trials, particularly in managing the placebo effect, a common challenge in psychedelic research.

Read more about Lykos Therapeutics.

What Do Researchers Measure?

Even though animals cannot verbalize their distress, their behavior and biological markers tell us a lot:

  • Motivation and Pleasure: Decreased interest in rewards (like sweetened water) or reduced exploration in new environments.
  • Social Interaction: Reduced engagement with peers.
  • Physiology: Elevated cortisol levels, the stress hormone, or changes in neural circuits involved in emotion and stress.

These indicators help researchers evaluate the efficacy of new treatments before advancing to human trials.

From the Cage to the Patient: Why It Matters

Animal models provide an essential foundation for understanding the biology of mood disorders and evaluating the risks and effects of new medications. However, there are limitations:

  • Human Complexity: Psychological and social factors contributing to depression cannot be replicated in animals.
  • Translational Gaps: What works in animals does not always work in humans, making rigorous clinical trials essential.

This is where tools like EMOBOT revolutionize how we track human patients in clinical trials.

What About Technology?

Traditional tools for measuring depression symptoms in human clinical trials often rely on periodic questionnaires. While standardized, these tools have their limitations.

EMOBOT, a cutting-edge MedTech innovation, offers a continuous, passive, and multimodal measurement of mood. Using artificial intelligence and diverse sensors, EMOBOT provides:

  • Real-Time Tracking: Capturing daily mood fluctuations instead of relying on isolated moments.
  • Reduced Bias: Avoiding sole dependence on patient self-reporting.
  • Richer, More Reliable Data: Integrating multiple signals (behavioral, physiological, etc.) for a comprehensive understanding of emotional states and treatment efficacy.

This approach represents a groundbreaking tool for clinical trials and could transform how psychiatry measures and monitors mood disorders.

Why Talk About This?

Because every treatment begins with little-known but critical phases. From stressed rats in a laboratory to human clinical trials and cutting-edge technologies like EMOBOT, each step plays a vital role in developing innovative therapies for mood disorders.

So, next time we’ll ask ourselves if rats will go maniac in Spring but for now let’s enjoy winter.

Sources

  • Willner, P. (1997). "Validity, reliability and utility of the chronic mild stress model of depression: A 10-year review and evaluation." Psychopharmacology.
  • Cryan, J. F., et al. (2005). "Animal models of depression: The necessity of translational approaches." Neuropsychopharmacology.
  • Cybin Phase 2 Results
  • Lykos and MDMA Therapy

More on the author

Tanel Petelot, CEO and co-founder of EMOBOT, is an engineer trained at UC Berkeley and École Centrale, passionate about mental health and therapeutic innovation. In 2022, he co-founded EMOBOT, a MedTech startup developing devices for continuous, passive, and multimodal mood measurement, using advanced AI-driven analysis of symptoms. The company partners with over 30 hospitals in Europe, where its solution is used in clinical trials, and is now expanding into the U.S.

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