Depressed Mice Study Is Inhumane and Clinically Irrelevant

The Physicians Committee

Beyond Animal Research

By Jonathan Balcombe, Ph.D.
March 2006

Depressed Mice Study Is Inhumane and Clinically Irrelevant

A study published in the prestigious journal Science reported on the apparent role of a protein (called p11) in fighting depression.1 However, most of the depressed subjects in this study weren’t people—they were mice.

Some of the mice were transgenic “knockout” mice lacking the protein in question. These mice are called “helpless” because when they are dangled by the tail for six minutes using adhesive tape (the “tail suspension test”) they show spontaneous helplessness (i.e., they don’t try to right themselves as much as mice that have the p11 protein). The study authors, who include Nobel laureate Paul Greengard, hope the work will ultimately lead to new depression treatments for people.

The treatment of the mice is depressing in itself. Aside from the genetic manipulations, animals (including some rats) received daily injections for up to four weeks, electroconvulsive treatment delivered by ear clip electrodes, and the tail suspension test. Killing methods involved decapitation under anesthesia, and focused microwave irradiation, in which a powerful microwave beam is aimed at the head of the restrained animal. Other techniques used fetal bovine serum (acquired by inserting a large needle into the heart of an unanesthetized fetal calf that is at least three months old and removed from a freshly slaughtered pregnant cow) and rabbit polyclonal antibodies (the production of which involves repeated injections and bleedings).

Importantly, the methods include no description of the animals’ housing, which plays an important role in the physical and psychological welfare of rodents. Typical lab housing conditions are cramped and barren, thwarting highly motivated natural behaviors, including hiding, foraging, burrowing, climbing, and choosing social partners. Some 50 percent of mice in lab cages develop stereotypic behaviors—functionless, repetitive movements linked to the frustration of important natural behaviors and thought to indicate psychological suffering.2

Not only is this study inhumane, it's unscientific. If we wanted to see if something caused headaches in people, we wouldn’t want them to be suffering headaches to begin with. It is common for animals in laboratories to suffer from baseline depression. How can we adequately assess “new” depression in an already depressed animal? That mice and rats cannot verbally report how they’re feeling is another serious drawback.

The study also found substantially lower p11 levels in human patients with depression, which raises the question: What are we really gaining from the mouse experiments? Because many of the procedures done to the mice would be considered unethical in humans, not all the findings for mice can be made for humans. But neurophysiological and behavioral differences between people and mice make extrapolation tenuous at best.

1. Svenningsson P, Chergui K, Rachleff I, Flajolet M, Zhang X, El Yacoubi M, Vaugeois J-M, Nomikos GG, Greengard P. Alterations in 5-HT1B receptor function by p11 in depression-like states. Science. 2006;311:77-80.
2. Mason GJ. Stereotypies and suffering. Behavioural Processes. 1991;25:103-115.