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the french surgeon henri laborit is known for his work on chlorpromazine ( rp4560 ) , a molecule from the rhne - poulenc pharmaceutical company , synthesized at the end of 1950 , and marketed as largactil at the end of 1952 .
laborit was a man of many talents , who considered that thinking and acting in directions opposite to common beliefs ( the doxa ) was a fruitful means of making discoveries , indeed , he made a series of significant discoveries in physiology and pharmacology .
he published several books on physiology and pharmacology , ethology and societal issues ; he was one of the innovative thinkers of the 20th century in france .
he repeatedly emphasized the fact that a better understanding of the cerebral determinants of human behaviors , such as dominance and aggression , is a necessary condition for any favorable evolution of human societies .
almost all of the 624 publications listed in medline with laborit as author are in french .
no tribute to his work has been published in english - speaking medical journals . in this article , several of laborit 's achievements will be described , and we will underline how the concept of inhibition of action might remain a worthwhile indicator for research on depression .
his father , a physician and officer in the french colonial troops , died from tetanus in 1920 . in spite of the sequelae of tuberculosis , which he had contracted at the age of 12 , laborit obtained a baccalaureate in paris and passed the exams of the school of naval medicine in bordeaux .
his first practice was as a navy physician , but , eager for better recognition , he turned to surgery .
his surgical work confronted him with patients dying during or after operations , and this motivated his research in anesthesiology ; this in turn led to the development of chlorpromazine , with publications in 1952 . in 1957 , laborit received the albert lasker clinical medical research award , together with six other researchers on reserpine and chlorpromazine . in 1958 , he opened his laboratory of eutonologie in the boucicaut hospital in paris .
he headed this laboratory until his death in 1995 , financing his research largely with the money obtained from patenting molecules .
he was editor in chief of the journal agressologie , published from 1955 to 1983 .
he gave lectures in many universities , on biology but also on town planning and human behavior , and from 1978 to 1983 , was invited as professor of biopsychosociology at the university of quebec . in 1981 , he received the anokhin prize from the soviet union , and in 1989 he accepted the chair of the institute of psychosomatics in torino , italy .
he also taught a seminar in lugano , switzerland , in conjunction with the university of san diego . from 1969 to 1976
he participated in the groupe des dix ( group of ten ) , a series of informal discussions between french personalities in the fields of politics , biological sciences , philosophy , and sociology .
it is said that this was because of the hostility of the parisian medical microcosm , notably the dean of the faculty of medicine , who could not accept the new views in anesthesiology and medicine that laborit proposed , and who made the journey to stockholm to dissuade the jury .
his wife was an anesthesiologist , and she shared the research work in the laboratory part time , the rest of her time being spent in anesthesiology , so as to support their family financially .
indeed , laborit only had a salary from the army and never had tenure in a french university .
in the field of pharmacology , aside from chlorpromazine , laborit worked on or discovered the neurotransmitter gamma - oh , the antidepressant minaprine , the sedative clomethiazole . in the field of anesthesiology , laborit studied a mix of an opiate analgesic and a hypnotic of the antihistamine class in order to induce a pharmacological disconnection of the neurovegetative system .
he considered that the nonspecific responses to stressors were in themselves toxic to the body : patients died in shock not because their defenses were exhausted , but because giving adrenaline to treat hypotension increased the dangers of the stress responses .
he wanted to shut down the stress response , since he saw that patients were killed by the endogenous mechanisms supposed to protect them from shock .
the laborit cocktail or cocktail lytique was the combination of promethazine , pethidine , and chlorpromazine , and this was later called neuroleptanalgesia . during surgical procedures ,
the patients were calm , still capable of obeying simple orders , and had fewer variations of blood pressure , although this effect of surgery did persist .
laborit developed further the technique of hypothermia , associated with chlorpromazine , and concluded that this provided protection against the toxicity of stress responses during anesthesia and surgery .
the indifference observed under chlorpromazine led to trials in agitated patients , by a small group of psychiatrists , advised by laborit .
jean delay and pierre deniker described the effects of the molecule in manic psychosis and mental confusion .
he was asked to do this by the army because of the toxicity of oxygen in divers .
the synthesis of gamma - oh emerged this work , with the intention of finding a -aminobutyric acid ( gaba)-like compound that would cross the blood - brain barrier .
the idea was that since glial cells had few mitochondria , and neurons had many , the former helped the latter , and neurons could be indirectly helped by facilitating the pentose pathway in glial cells .
gamma - oh was used in delirium tremens , in anesthesia after head trauma , in insomnia , and is still prescribed in narcolepsy .
the antidepressant agr 1240 ( minaprine , marketed as cantor until 1990 ) was a stimulating molecule that laborit developed with the idea of neutralizing the consequences of inhibition of action .
there is inhibition of action when behaviors become impossible , and this is deleterious to health .
this happens when an instinctive behavior ( such as fight or flight ) is impossible , when acting is useless , when a danger can not be predicted , or when no previous response pattern exists to direct action . in these situations , a brain system , the systme inhibiteur de l'action , or behavioral inhibition system ( bis ) ,
is activated and stimulates the neuroendocrine responses that were described by walter cannon in the 1920s and hans selye in the 1930s and 1940s .
inhibition of action is illustrated in animal experiments that we carried out in laborit 's laboratory during the early 1970s .
rats received 10 cycles of 21 plantar electric shocks daily for 1 week , each shock session being preceded by a light and sound warning stimulus . in these conditions , if the animal could carry out an active avoidance ( when the other compartment was open ) , or if the rat was placed with another rat and could fight with it , no arterial hypertension was observed .
if the rat could not escape or fight , hypertension developed that remained chronic for 1 month .
follow - up of these rats showed that they remained hypertensive 3 months later ( kunz , unpublished ) . in another experiment , all rats received shocks from which they could not escape .
half of them were subjected to convulsions ( induced electrically ) after each shock session and did not develop hypertension .
this lack of hypertension was interpreted as being due to the impossibility- of conditioned learning because of the convulsions .
the bis ( median septal area , hippocampus , lateral amygdala and ventromedial hypothalamus ) could be at the origin of peripheral vasomotor disorders , while the central activating systems , or behavioral activating systems ( bas  medial forebrain bundle and paraventricular system ) would prevent these effects .
a film was made based on laborit 's theories : mon oncle d'amrique ( my american uncle ) by the french film maker alain resnais ( 1980 ) .
the film contains explanations by laborit ( box i ) , as well as scenes of the rat experiments described above .
the main theme of the movie was that achieving the right equilibrium between action and inhibition of action is paramount to mental and physical health .
fleeing is the solution to escape inhibition of action , when other behaviors are not possible .
responses to one 's environment , when dysfunctional , become toxic , as laborit studied in the 1950s in the field of anesthesia .
he later studied the behavior of rats and concluded that inhibition of action induced pathogenic mechanisms .
he observed that humans have ancestral instinctive behavioral responses that are not adapted to the modern societal milieu .
his aim was to explain biology and behavior at each of the different levels of functioning , from cell to society .
the concept of inhibition of action remains operative in the search for new psychotropic medications , which could counterbalance unfavorable endogenous defense reactions .
mon oncle d'amrique ( my american uncle )   in this 1980 movie by alain resnais , laborit explains several of his ideas .
the film was a success , but some critics considered laborit 's declarations to be too reductionist . a being exists only in order to be .
[ ... ] animals [ ... ] have to act within a space . and to do this , they need a nervous system .
this nervous system allows the animal to act within and on the environment , always with the same purpose - to ensure survival .
[ ... ] the purpose of a brain is not to think , but to act .
[ ... ] there is a first brain , which maclean called reptilian , the brain of reptiles .
it triggers behaviors associated with immediate survival , without which the animal could not survive [ ... ] a second brain is added to the first and is usually called the brain of memory . without a memory of what is pleasant or unpleasant , there is no way of feeling happiness , sadness , distress , anger or love .
 a third brain is added to the first two : the cerebral cortex . in humans
it means that this third brain associates the underlying neural pathways , which bear the trace of past experiences , and combines them differently from the way they were imprinted by the environment at the time of the experience itself .
the first two operate unconsciously - we do not know what they have us do .
the third brain gives us an explanatory language , which always provides an excuse , an alibi , for the unconscious functioning of the first two brains .
the second is a behavior of gratification  when we experience an action that yields pleasure , we try to repeat it .
the third is a behavior in response to punishment , either by flight to avoid it or by fight to destroy the source of aggression .
the last is a behavior of inhibition : no movement , tense waiting , rising anxiety .
anxiety marks the impossibility of mastering a situation . [ ... ] when two individuals have different plans or the same plan and compete to carry it out , there is a winner and a loser .
seeking dominance , in a space one can call the territory , is the fundamental basis of all human behaviors , the motivation of this being wholly unconscious .
there is simply the process whereby , through the nervous system , the individual learns to keep for himself an object or a being that is also wanted , coveted by another being .
and the individual knows , through this learning process , that in this competitive situation if he wants to hold onto the object or being , he must dominate .
[ ... ] through language humans have been able to transmit from generation to generation all the experience they have acquired over millennia [ ... ] in other words , our instinctive urges and our cultural reflexes will be masked by language , by a logical argument .
language therefore helps hide the cause of dominance , the underlying mechanisms , and the establishment of dominance .
it makes the individual believe that by working for the common good he will experience his own pleasure . whereas , in general , all he does is to maintain hierarchical situations that are obscured by linguistic alibis , which in a way serve him as an excuse .
the construction worker who every day sees a site foreman he detests ca n't punch him in the face , because someone will call the police .
he ca n't quit because he 'd be unemployed and every day of his life , every week in the month , every month in the year , as the years go by , he is subject to inhibition of action .
this leads to an explosion of aggression which is rarely productive but which , in terms of the nervous system , is perfectly explicable .
so , it 's worth repeating , this situation in which an individual can find himself , this inhibition of action , if it persists , induces pathological situations .
the biological perturbations accompanying it will trigger physical diseases and all the behaviors associated with mental illness . [ ... ] the unconscious mind is a fearsome instrument .
not so much because of its repressed content [ ... ] but because of everything that is , on the contrary , authorized ( reward ) and sometimes even rewarded by the social culture that has been implanted in the brain since birth , of the presence of which the person is unaware .
yet it is the unconscious that guides this person 's actions [ ... ] what is called the personality is constructed from a mishmash of value judgments , prejudices , and commonplaces which weigh heavily and which , with age , become ever more inflexible , increasingly unquestioned . and when a single brick in the edifice is removed , when the edifice collapses and the person discovers anxiety , then this anxiety will express itself even if it means murder , in the case of an individual , or genocide or war , for social groups . here
we begin to understand by what mechanisms , why and how , through history and in the present , hierarchical scales of dominance are established .
as long as people on this planet remain unaware of how their brain works and how they use it , as long as it has not been said that hitherto it has always been to dominate others , there is little chance that anything will change .
copyright maria laborit , jacques laborit , jean laborit , marie - nolle benoit - laborit .
henri laborit was one of the founders of modern neuropsychopharmacology , having discovered , or participated in , the discovery of chlorpromazine , gamma - oh , clomethiazole , and minaprine . 
 he also put forward a theory regarding the necessity of counteracting the negative consequences of defense mechanisms during anesthesia or behavioral inhibition . 
 the scope of his work covers neurophysiology , pharmacology , psychiatry , and psychosomatics . 
 his independence of spirit meant that most of his research was not done within university settings .