When Anger Turns Inward

“A living being is a memory which acts” —Henri Laborit

Alain Resnais was a director obsessed with translating memory into film; Hiroshima mon amour and Last Year in Marienbad are well-known examples. A less obvious example is a strange film, part fiction, part non-fiction, starring the French physiologist Henri Laborit, called Mon oncle d’Amérique (My American Uncle). The film inter-cuts Laborit’s experiments and theories and draws analogies between the behavior of his lab rats and the humans in the story to question the idea of free will.

The lives of three seemingly disconnected characters are interwoven, and their behaviors around consumption, gratification, combat, and inhibition are explained biologically. At one point Laborit summarizes his grand theory of “inhibition de l’action”: If you do not have the possibility of dominating the situation, nor the possibility of fleeing, then you are inhibited in your action, and the stress is turned inward. You become aggressive but against yourself.1

In the 1970s Laborit found that when he subjected rats to chronic stress—electric shocks from which they could not escape—over the course of a week, it led to detrimental physiological changes that persisted long after the shocks had ceased. Yet if the animal was free to act—if the rat could flee to the safe side of the cage—or if two rats were placed in a cage and could fight each other, then their physiology remained intact.2

He proposed that when dealing with chronic stress, “inhibition of action,” the inability to fight or flee, transmuted into a self-destructive force. Laborit was a controversial figure, and in the film his explanation of the brain is outdated in parts. But the methods Laborit used to study stressed rodents in the 1970s are echoed today in studies for depressed humans.

To study depression, you need a model. You need a depressed mouse. If you take an antidepressant (as 11% of people in the United States do3^,4), then Laborit’s stressed mouse is your ancestral guinea pig. You are part of this chain. In these studies, mice are exposed to a barrage of environmental stressors such as tilting cages, shifting light cycles to create sleep disturbance, and alternating periods of crowding and isolation under a protocol called “Chronic Social Defeat Stress.”5 It leverages an organism’s natural territory defense behaviors to create a profound traumatic psychosocial stressor.

A smaller, more docile “intruder” mouse is introduced into the home cage of larger, highly aggressive, territorially dominant “resident” mouse. The resident attacks the intruder for five to ten minutes before they are separated by a perforated, transparent divider for the rest of the day. The defeated mouse is now physically safe but continues to be exposed to visual, auditory, and olfactory threat cues from its attacker. This process is repeated for ten days with ten different resident aggressors to prevent habituation. The stress should be unpredictable and inescapable.

This method only is effective if the mice are male, as female mice are not usually violent toward each other. How do you make a female mouse depressed? Make her watch the males fight.6 It is estimated that women are prescribed antidepressants at double the rate of men.7 The instrumentalization of these models reinforces Laborit’s idea that if an organism cannot act to fight or flee, the aggression is turned inward, leading to a physiological portrait that resembles depression.

The most commonly prescribed antidepressants, around 64%, are a class of drugs called selective serotonin reuptake inhibitors (SSRIs). SSRIs increase serotonin, so for many decades the theory of depression was neurotransmitter based. If SSRIs work by increasing serotonin, then surely depression was due to its lack. The accidental discovery of antidepressants and the subsequent monoamine theory of depression kept researchers focused, for many years, on neurotransmitters and the neurons that contain them as defective loci that needed to be corrected.8

More recently, both mouse and human studies have shifted attention toward the environment around the neuron, an active molecular scaffold called the extracellular matrix (ECM). This matrix shows differences in stressed and depressed subjects that can be reversed with anti-depressant treatment. It is thought that changes in the ECM around the neuron affect the neuron’s activity and plasticity.9

Laborit’s fascination with stress began as a naval surgeon when he was trying to prevent post-operative shock, which is not caused by the surgery itself but the body’s reaction to it. The core of Resnais’s film Mon oncle d’Amérique uses Laborit’s ideas to question how much control, if any, we have over our reactions, from the molecular to the behavioral.

Most of this odd film is set in France, but it ends at a mural in the Bronx, with increasingly magnified frames of a forest painted on the side of a building. The trees dissolve into pixels of bricks. For me, it evokes peering down the microscope at neurons for hours, beyond their dendritic arbors, to the scale of molecule clusters, looking for clues.

Maybe it is too reductionist to take observations in the lab and apply them to society. But Laborit’s work reveals that when anger is inhibited—by choice or circumstance—it doesn’t go away. Instead it reflects inwards, its forces ramifying, like the ending of Resnais’s film as it moves across scales, from the social environment down to the most elemental parts of our world and ourselves. And if we zoom back out, just as it is for our neurons, it might be worth examining what surrounds us.