748 lines
57 KiB
HTML
748 lines
57 KiB
HTML
<html>
|
|
<head><title>Intelligence and metabolism</title></head>
|
|
<body>
|
|
<h1>
|
|
Intelligence and metabolism
|
|
</h1>
|
|
|
|
<p>
|
|
<hr />
|
|
<hr />
|
|
</p>
|
|
|
|
<p>
|
|
<strong>Appropriate stimulation is an essential part of the developmental process. Inappropriate stimulation
|
|
is a stress that deforms the process of growth. Mediators of stress, such as serotonin, can cause
|
|
persistent distortions of physiology and behavior.</strong>
|
|
</p>
|
|
<p>
|
|
<strong>Education can either activate or suppress mental energy. If it is mainly obedience training, it
|
|
suppresses energy. If it creates social dislocations, it disturbs mental and emotional energy.</strong>
|
|
</p>
|
|
<p>
|
|
<strong>Stress early in life can impair learning, cause aggressive or compulsive behavior, learned
|
|
helplessness, shyness, alcoholism, and other problems.</strong>
|
|
</p>
|
|
<p>
|
|
<strong>Serotonin activates the glucocorticoid system, which can produce brain atrophy. Antiserotonin agents
|
|
protect against brain atrophy and many other effects of stress. The brain-protecting neurosteroids,
|
|
including pregnenolone and progesterone, which are increased by some kinds of stimulation, are decreased
|
|
by isolation stress, and in their absence, serotonin and the glucocorticoids are relatively unopposed.
|
|
</strong>
|
|
</p>
|
|
<p>
|
|
<strong>Since excess serotonin can cause thrombosis and vasospasms, and the excess cortisol resulting from
|
|
hyperserotonemia can weaken blood vessels and the immune system, a person's longevity is likely to be
|
|
shortened if something doesn't intervene to alter the patterns induced by stress early in life.</strong>
|
|
</p>
|
|
|
|
<p>
|
|
<hr />
|
|
<hr />
|
|
</p>
|
|
<p>
|
|
<strong>Baroness Blatch: "My Lords, the levels of achievement are well above the national average of our own
|
|
state schools."
|
|
</strong>
|
|
</p>
|
|
<p>
|
|
<strong>"This is a school which attained 75 per cent A to C passes in 1998, and 63.9 per cent in 1999. Those
|
|
figures are well above national averages. There is no truancy; and there is the highest possible level
|
|
of parental satisfaction with the school. When those parents are paying their money and know what they
|
|
are paying for, who are we to take a different view about the philosophy of education in a private
|
|
school?"</strong>
|
|
</p>
|
|
<p>
|
|
<strong>Comment during debate in House of Lords, June 30, 1999, on Chief Inspector of Schools Woodhead's
|
|
threat to close Summerhill, a democratic school which had been started in 1921.
|
|
</strong>
|
|
</p>
|
|
<p>
|
|
<strong>In 1927, the government inspectors had recommended that 'all educationalists' should come to
|
|
Summerhill to see its 'invaluable' research, which demonstrated that students' development is better
|
|
when they regulate themselves and are not required to attend lessons.</strong>
|
|
</p>
|
|
|
|
<p>
|
|
<hr />
|
|
<hr />
|
|
</p>
|
|
<p>
|
|
Having written about animal intelligence, and the ways in which it is similar to human intelligence, now I
|
|
want those ideas to serve as a context for thinking about human intelligence without many of the usual
|
|
preconceptions.
|
|
</p>
|
|
<p>
|
|
Intelligence is an interface between physiology and the environment, so it's necessary to think about each
|
|
aspect in relation to the other. Things, both biochemical and social, that enhance intelligence enhance life
|
|
itself, and vice versa.
|
|
</p>
|
|
<p>
|
|
Psychologists have tried to give their own definitions to words like idiot, imbecile, moron, and genius, but
|
|
they have just been refining the clich"s of the culture, in which "dummy" is one of the first words that
|
|
kids in the U.S. learn. Many psychologists have tried to create "culture-free" tests of intelligence, making
|
|
it clear that they believe in something like innate animal intelligence, though they usually call it
|
|
"genetic" intelligence. Other psychometrists have transcended not only biology but even rationality, and
|
|
have catalogued the <strong><em>preferences</em></strong>
|
|
|
|
of people that they define as intelligent, and designed "I.Q. tests" based on the selection of things that
|
|
were preferred by "intelligent people." This behavior is remarkably similar to the "psychometry" of the
|
|
general culture, in which "smart" people are those who do things the "right" way.
|
|
</p>
|
|
<p>
|
|
About thirty years ago, someone found that the speed with which the iris contracts in response to a flash of
|
|
light corresponds very closely to the I.Q. measured by a psychologist using a standard intelligence test.
|
|
The devices used to measure reaction time in drivers' education courses also give a good indication of a
|
|
person's intelligence, but so does measuring their heart rate, or taking their temperature. Colleges would
|
|
probably be embarrassed to admit students on the basis of their temperature (though they commonly award
|
|
scholarships on the basis of the ability to throw a ball). Colleges, to the extent that they are serious
|
|
about the business of education, are interested in the student's ability to master the culture.
|
|
</p>
|
|
<p>
|
|
The way a person has learned during childhood can shape that person's manner of grasping the culture. To
|
|
simply accelerate the learning of a standard curriculum will increase that person's "I.Q." on a conventional
|
|
test, but the important issue is whether it is really intelligent to learn and to value the things taught in
|
|
those curricula. Some educators say that their purpose is to socialize and indoctrinate the students into
|
|
their discipline, others believe their purpose is to help their students to develop their minds. Both of
|
|
these approaches may operate within the idea that "the culture" is something like a museum, and that
|
|
students should become curators of the collection, or of some part of it. If we see the culture
|
|
metaphorically as a mixture of madhouse, prison, factory, and theater, the idea of "developing the student's
|
|
mind" will suggest very different methods and different attitudes toward "the curriculum"
|
|
</p>
|
|
<p>
|
|
Even sophisticated people can fall into stereotyped thinking when they write about issues of intelligence.
|
|
For example, no one considers it a sign of genius when a slum kid is fluent in both Spanish and English, but
|
|
when some of history's brightest people are discussed, the fact that they learned classical Greek at an
|
|
early age is always mentioned. No one mentions whether they were competent in idiomatic Spanish.
|
|
</p>
|
|
|
|
<p>
|
|
One of the old cultural stereotypes is that child prodigies always "burn out," as if they were consuming a
|
|
fixed amount of mental energy at an accelerated rate. (This idea of burn-out is isomorphic with the other
|
|
cultural stereotypes relating aging to the "rate of living," for example that people with slow heart beats
|
|
will live longer.) Some of the men who have been considered as the world's brightest have, in fact, gone
|
|
through a crisis of depression, and Terman's long-term study of bright people found that "maladjustment" did
|
|
increase with I.Q., especially among women. But the facts don't support the concept of "burn-out" at all. I
|
|
think the facts reveal instead a deep flaw in our ideas of education and professional knowledge.
|
|
</p>
|
|
<p>
|
|
In a world run by corporation executives, university presidents ("football is central to the university's
|
|
mission"), congressmen, bankers, oilmen, and agency bureaucrats, people with the intelligence of an ant (a
|
|
warm ant) might seem outlandishly intelligent. This is because the benighted self-interest of the
|
|
self-appointed ruling class recognizes that objective reality is always a threat to their interests. If
|
|
people, for example, realized that estrogen therapy and serotonin-active drugs and x-rays and nuclear power
|
|
and atomic bomb tests were beneficial only to those whose wealth and power derive from them, the whole
|
|
system would lose stability. Feigned stupidity becomes real stupidity.
|
|
</p>
|
|
<p>
|
|
But apart from ideologically institutionalized stupidity, there are real variations in the ability to learn,
|
|
to remember and to apply knowledge, and to solve problems. These variations are generally metabolic
|
|
differences, and so will change according to circumstances that affect metabolism. Everyday social
|
|
experiences affect metabolism, stimulating and supporting some kinds of brain activity, suppressing and
|
|
punishing others. All of the activities in the child's environment are educational, in one way or another.
|
|
</p>
|
|
<p>
|
|
Some of the famous prodigies of history illustrate the importance of ideology in the development of
|
|
intellect. Family ideology, passing on the philosophical orientations of parents and their friends, shapes
|
|
the way the children are educated.
|
|
</p>
|
|
<p>
|
|
Some of these family traditions can be traced by considering who the child's godfather was. Jeremy Bentham
|
|
was John Stuart Mill's godfather, Mill was Bertrand Russell's; Ralph Waldo Emerson was William James'
|
|
godfather, James was W. J. Sidis's. Willy Sidis was educated by his parents to demonstrate their theory of
|
|
education, which grew out of the philosophies of Emerson and James. His father, Boris Sidis, was a pioneer
|
|
in the study of hypnosis, and he believed that suggestion could mobilize the mind's "reserve energy." Willy
|
|
learned several languages and advanced mathematics at an early age. After he graduated from Harvard at the
|
|
age of 16, he tried teaching math at Rice Institute, but he was displeased by the attitudes of his students
|
|
and of the newspaper and magazine writers who made a profession of mocking him. He attended law school at
|
|
Harvard, and would have been imprisoned as a conscientious objector if the war hadn't ended.
|
|
</p>
|
|
<p>
|
|
Antisemitism probably played a role in his sense of isolation when he was at Harvard and Rice. In 1912 Henry
|
|
Goddard, a pioneer in intelligence testing (and author of <strong><em>The Kallikak Family: A Study in the
|
|
Heredity of Feeble- Mindedness</em>)</strong>, administered intelligence tests to immigrants and
|
|
determined that 83 percent of Jews and 87 percent of Russians were "feeble-minded." By the standards of the
|
|
time, it was highly inappropriate for the child of extremely poor Jewish immigrants from eastern Europe to
|
|
be so bright.
|
|
</p>
|
|
<p>
|
|
Sidis hid from the press, and worked as a bookkeeper and clerk, while he studied and wrote. During his years
|
|
of obscurity, he wrote books on philosophy and American history. Eventually, the journalists discovered him
|
|
again, and after prolonged lawsuits against the magazines for invasion of privacy and slander, he died of a
|
|
stroke at the age of 46.
|
|
</p>
|
|
<p>
|
|
Sidis is probably the culture's favorite example of the child prodigy who burns out, but people (Robert
|
|
Persig, Buckminster Fuller) who have read his books have said favorable things about them. The journalists'
|
|
emphasis on the fact that Sidis never held a prestigious job nicely illustrates their clich" mentality: "If
|
|
you're so smart, why aren't you rich?" But throughout history, intelligent nonconformists have supported
|
|
themselves as craft-workers or technicians--Socrates as a stone mason, Spinoza as a lens grinder, Blake as
|
|
an engraver, Einstein as a patent examiner, for example.
|
|
</p>
|
|
|
|
<p>
|
|
In conventional schools (as in conventional society) 10,000 questions go unanswered, not only because a
|
|
teacher with many students has no time to answer them, but also because most teachers wouldn't know most of
|
|
the answers.
|
|
</p>
|
|
<p>
|
|
The parents of W. J. Sidis and J. S. Mill were remarkably well educated people who, because they dissented
|
|
from society's ideology, chose to spend much of their time educating their children. Whenever a question
|
|
about Euclidean geometry or Greek grammar occurred to the child, it could be answered immediately. It was
|
|
only natural that progress would be fast, but there were more important differences.
|
|
</p>
|
|
<p>
|
|
When questions are answered, curiosity is rewarded, and the person is enlivened. In school, when following
|
|
instructions and conforming to a routine is the main business, many questions must go unanswered, and
|
|
curiosity is punished by the dulling emptiness of the routine.
|
|
</p>
|
|
<p>
|
|
Some schools are worse than others. For example, slum children were given I.Q. tests when they started
|
|
school, and each subsequent year, and their I.Q.s dropped with each year of school. In a stimulating
|
|
environment, the reverse can happen, the I.Q. can rise each year. Since the tests aren't "culture free,"
|
|
their scores reflected the material that they were being taught, but they undoubtedly also reflected the
|
|
increasing boredom and despair of the children in a bad school, or the increasing liveliness of the children
|
|
in the stimulating environment.
|
|
</p>
|
|
<p>
|
|
I have spoken with people in recent years who still held the idea of a fixed genetic mental potential, who
|
|
believe that poor children fall behind because they are reaching their "genetic limit." For them, the I.Q.
|
|
represents an index of intrinsic quality, and is as important as distinguishing between caviar and frogs'
|
|
eggs. The rat research of Marion Diamond and others at the University of California, however, showed that
|
|
the structure, weight, and biochemistry of a rat's brain changes, according to the amount of environmental
|
|
stimulation and opportunity for exploration. This improvement of brain structure and function is passed on
|
|
to the next generation, giving it a head-start. It isn't likely that rats are more disposed than humans to
|
|
benefit from mental activity, and in the years since Diamond's research there have been many discoveries
|
|
showing that brains of all sorts complexify structurally and functionally in response to stimulation.
|
|
</p>
|
|
|
|
<p>
|
|
Rats isolated in little boxes, generation after generation--the normal laboratory rats--were the standard,
|
|
but now it's known that isolation is a stress that alters brain chemistry and function.
|
|
</p>
|
|
<p>
|
|
Willy Sidis and John Stuart Mill were being stimulated and allowed to develop in one direction, but they
|
|
were being isolated from interaction with their peers. When Mill was twenty he went into a depression, and
|
|
later he wrote that it was because he discovered that he was unable to <strong><em>feel.</em></strong> He
|
|
had developed only part of his personality.
|
|
</p>
|
|
<p>
|
|
Bertrand Russell (1872-1970), orphaned at the age of four, went to live with his grandmother, who chose not
|
|
to send him to school, but provided tutors. He didn't experience a sense of academic pressure, and was able
|
|
to read whatever he wanted in his late grandfather's library. He didn't realize that he was unusually bright
|
|
until he went to Cambridge. The unusual freedom of his childhood must have contributed to his willingness to
|
|
hold unpopular opinions. In 1916 he was fined, and in 1918 imprisoned for 6 months, for opposing the war.
|
|
</p>
|
|
|
|
<p>
|
|
In 1927, Russell and his wife, Dora Black, started a school. He later wrote that, although the average
|
|
student at the school was very bright, an exceptionally bright student was likely to be ostracized by the
|
|
less bright students. He commented on the harm done to the brightest students by their social isolation,
|
|
probably thinking about his own education in relative isolation. A psychologist (Leta Hollingworth, 1942)
|
|
has made similar observations about the isolation that can be produced by a large difference of I.Q. She did
|
|
a series of studies of very bright children, beginning in 1916, including working with some of them in a
|
|
program she designed in a New York public school. Her empathy allowed her to discover things that weren't
|
|
apparent to her contemporaries.
|
|
</p>
|
|
<p>
|
|
During this time Lewis Terman was studying bright children, and wanted to disprove some of the popular
|
|
stereotypes about intelligent people, and to support his ideology of white racial superiority. In 1922 he
|
|
got a large grant, and sorted out about 1500 of the brightest children from a group of 250,000 in
|
|
California. He and his associates then monitored them for the rest of their lives (described in <strong><em
|
|
>Genetic Studies of Genius</em></strong>). His work contradicted the stereotype of bright people as
|
|
being sickly or frail, but, contrary to his expectation, there was an association between maladjustment and
|
|
higher I.Q.; the incidence of neurotic fatigue, anxiety, and depression increased along with the I.Q. The
|
|
least bright of his group were more successful in many ways than the most bright. He didn't really confront
|
|
the implications of this, though it seriously challenged his belief in a simple genetic racial superiority
|
|
of physique, intellect, and character.
|
|
</p>
|
|
<p>
|
|
I.Q. testing originated in a historical setting in which its purpose was often to establish a claim of
|
|
racial superiority, or to justify sterilization or "euthanasia," or to exclude immigrants. More recently,
|
|
the tests have been used to assign students to certain career paths. Because of their use by people in power
|
|
to control others, the I.Q. tests have helped to create misunderstanding of the nature of intelligence. A
|
|
person's "I.Q." now has very strong associations with the ideology of schooling as a road to financial
|
|
success, rather than to enrichment of a shared mental life.
|
|
</p>
|
|
<p>
|
|
If a bad school resembles, on the intellectual level, a confining rat box, the educational isolation of
|
|
Mill, Russell, and Sidis was emotionally limiting, almost like solitary confinement. Once when Willy Sidis
|
|
was arrested for marching in a May Day parade, his father was able to keep him from going to prison, but
|
|
Willy apparently would have preferred the real prison to life with his parents.
|
|
</p>
|
|
|
|
<p>
|
|
None of these three famous intellects was known for youthful playfulness, though playfulness is a quality
|
|
that's closely associated with intelligence in mammals and birds. (Russell, however, in middle age developed
|
|
many new interests, such as writing short stories, and had many new loves even in old age.) Stress early in
|
|
life, such as isolation, reduces the playfulness of experimental animals. Playfulness is contagious, but so
|
|
is the inability to play.
|
|
</p>
|
|
<p>
|
|
In schools like Summerhill, which was founded in 1921 by A. S. Neill, students aren't required to attend
|
|
classes when they would rather do something else, but at graduation they usually do better on their
|
|
standardized national examinations than students who have dutifully attended classes for years. For
|
|
students, as for rats, freedom and variety are good for the brain, and tedious conformity is harmful. When a
|
|
school is very good, it can spread a contagion of playfulness along with an interest in learning.
|
|
</p>
|
|
<p>
|
|
An environment that fosters optimal intelligence will necessarily promote the development of emotional
|
|
health, and will almost certainly foster good physical health and longevity, because no part of the
|
|
physiological system can thrive at the expense of another part. And within the boundaries of life-enriching
|
|
environments, there are infinite possibilities for variety.
|
|
</p>
|
|
<p>
|
|
There is a common belief in the rigidity of the adult nervous system, in analogy with feral cats or dogs,
|
|
that supposedly can't be tamed if they have grown up without knowing humans. But people who have had the
|
|
inclination to understand wild animals have found that, even when the animals have been captured as adults,
|
|
they can become as sociable as if they had grown up in domestication. The "horse whisperer" demonstrated
|
|
this sort of empathetic approach to animals. Sometimes, these people have a similar ability to communicate
|
|
with people who are retarded, or autistic, or demented, but the professionalization of society has made it
|
|
increasingly unlikely that people with the need for intuitive help will encounter someone who is able to
|
|
give it. The closest psychology has come to professionally recognizing the importance of empathy was in Carl
|
|
Rogers' work, e.g., <em>
|
|
Client-Centered Therapy.</em>
|
|
</p>
|
|
<p>
|
|
Rogers showed that a sense of solidarity must exist between therapist and client for the therapy to be
|
|
helpful. A similar solidarity has to exist between teacher and student, for education to be successful. If
|
|
ordinary family and social contacts could occur within such an atmosphere of mutual respect, psychopathology
|
|
(including learning difficulties) would be much less common.
|
|
</p>
|
|
<p>
|
|
Although three individuals don't prove an argument, I think the lives and situations of Sidis, Mill, and
|
|
Russell are usefully symbolic. Sidis, who grew up under intense pressure and social isolation and in extreme
|
|
poverty, died at the age of 46. Mill, who was educated mainly by his father, in secure financial
|
|
circumstances, experienced social isolation and moderate pressure, and lived about 20 years longer than
|
|
Sidis did. Russell, who grew up in the highest circles of the ruling class, experienced no pressure, and
|
|
only the mild kind of social isolation that wasn't exceptional for his class. He lived to be 97.
|
|
</p>
|
|
<p>
|
|
The psychopathology of social isolation has been studied in a variety of animals, and many features are
|
|
similar across species, including humans. Aggression, helplessness, and reduced ability to learn are
|
|
typically produced in animals by social isolation, and it's clear that certain kinds of family environment
|
|
produce the same conditions in children. Schools seldom help, and often hinder, recovery from such early
|
|
experiences.
|
|
</p>
|
|
<p>
|
|
"Vital exhaustion," decreased slow wave sleep, and anger, which are associated with the "type A personality"
|
|
and with circulatory and heart disease, appear to have their origin in childhood experiences. Low income and
|
|
financial insecurity are strongly associated with anger, sleep disturbances, and circulatory disease. In
|
|
animals stressed by social isolation, similar features emerge, under the influence of decreased
|
|
neurosteroids, and increased serotonin and activity of the glucocorticoid system.
|
|
</p>
|
|
<p>
|
|
The "smart drug" culture has generally been thinking pharmaceutically rather than biologically. Behind that
|
|
pharmaceutical orientation there is sometimes the idea that the individual just isn't trying hard enough, or
|
|
doesn't have quite the right genes to excel mentally.
|
|
</p>
|
|
<p>
|
|
Many stimulants--amphetamine and estrogen, for example--can increase alertness temporarily, but at the
|
|
expense of long range damage. The first principle of stimulation should be to avoid a harmful activation of
|
|
the catabolic stress hormones. Light, play, environmental variety and exploratory conversations stimulate
|
|
the whole organism in an integral way, stimulating repair processes and developmental processes.
|
|
</p>
|
|
<p>
|
|
Any chemical support for intelligence should take into account the mind-damaging stresses that our culture
|
|
can impose, and provide defense against those. In darkness and isolation, for example, the stress hormones
|
|
increase, and the brain-protective steroids decrease. The memory improvement that results from taking
|
|
pregnenolone or thyroid (which is needed for synthesizing pregnenolone from cholesterol) is the result of
|
|
turning off the dulling and brain-dissolving stress hormones, allowing normal responsiveness to be restored.
|
|
</p>
|
|
<p>
|
|
If we know that rats nurtured in freedom, in an interesting environment, grow more intelligent, then it
|
|
would seem obvious that we should experiment with similar approaches for children--if we are really
|
|
interested in fostering intelligence. And since violence and mental dullness are created by the same social
|
|
stresses, even the desire to reduce school violence might force the society to make some improvements that
|
|
will, as a side effect, foster intelligence.
|
|
</p>
|
|
|
|
<p><h3>REFERENCES</h3></p>
|
|
<p>
|
|
B. Russell: "If you wish to know what men will do, you must know not only or principally their material
|
|
circumstances, but rather the whole system of their desires with their relative strengths."
|
|
</p>
|
|
<p>
|
|
John Holt, from an interview in <em>Mother Earth News,</em> July/August, 1980<strong>:</strong>
|
|
"I suggested that we simply provide young people with schools where there are a lot of interesting things to
|
|
look at and work with . . . but that we let the chidlren learn in their own wqys. If they have questions,
|
|
answer the questions. If they want to know where to look for something, show them where to look."
|
|
</p>
|
|
<p>
|
|
John Holt, from the introduction to his book, <em>Teach Your Own,</em> (New York: Dell, 1981)<strong
|
|
>:</strong> "The children in the classroom, despite their rich backgrounds and high I.Q.'s, were with few
|
|
exceptions frightened, timid, evasive, and self-protecting. The infants at home were bold adventurers."
|
|
</p>
|
|
|
|
<p>
|
|
"It soon became clear to me that children are by nature and from birth very curious about the world around
|
|
them, and very energetic, resourceful, and competent in exploring it, finding out about it, and mastering.
|
|
In short, much more eager to learn, and much better at learning, than most adults. Babies are not blobs, but
|
|
true scientists. Why not then make schools into places in which children would be allowed, encouraged, and
|
|
(if and when they asked) helped to explore and make sense of the world around them (in time and space) in
|
|
ways that most interested them?"
|
|
</p>
|
|
<p>
|
|
Psychosom Med 1984 Nov-Dec;46(6):546-8. <strong>Rapid communication: whole blood serotonin and the type A
|
|
behavior pattern.</strong> Madsen D, McGuire MT.<strong>
|
|
In 72 young males, whole blood serotonin is shown to have a pronounced relationship with the Type A
|
|
behavior pattern.</strong> The relationship is explored with multivariate statistical techniques.
|
|
</p>
|
|
<p>
|
|
J Neurochem. 2000 Aug;75(2):732-40. Serra M, Pisu MG, Littera M, Papi G, Sanna E, Tuveri F, Usala L, Purdy
|
|
RH, Biggio G.<strong>
|
|
Social isolation-induced decreases in both the abundance of neuroactive steroids and GABA(A) receptor
|
|
function in rat brain.</strong>
|
|
</p>
|
|
|
|
<p>
|
|
Ann Med 2000 Apr;32(3):210-21. <strong>Role of serotonin in memory impairment.</strong> Buhot MC, Martin S,
|
|
Segu L.
|
|
</p>
|
|
<p>
|
|
Ivan Illich and Etienne Verne, <strong><em>Imprisoned in the global classroom.</em></strong>
|
|
London, Writers and Readers Publishing Cooperative, 1976.
|
|
</p>
|
|
<p>
|
|
Ivan Illich, <strong><em>Deschooling society.</em></strong> Harmondsworth: Penguin, 1976 (1971).
|
|
</p>
|
|
|
|
<p>
|
|
----Tools for Conviviality<em> </em>(1973).
|
|
</p>
|
|
<p><strong><em>----Toward a history of needs.</em></strong> New York, Pantheon Books, c1978.</p>
|
|
<p>
|
|
----Limits to medicine. medical nemesis : the expropriation of health. Harmondsworth New York, Penguin,
|
|
1977.
|
|
</p>
|
|
<p>
|
|
<strong><em>----Celebration of awareness: a call for institutional revolution.</em></strong> Harmondsworth,
|
|
Penguin Education, 1976. Pelican books Originally published: Garden City [N.Y.]: Doubleday, 1970; London:
|
|
Calder and Boyars, 1971.
|
|
</p>
|
|
|
|
<p><strong><em>----Disabling professions.</em></strong> London, Boyars, 1977, Ideas in progress series.</p>
|
|
<p>
|
|
Eur J Pharmacol 1992 Feb 25;212(1):73-8. <strong>5-HT3 receptor antagonists reverse helpless behaviour in
|
|
rats.</strong> Martin P, Gozlan H, Puech AJ Departement de Pharmacologie, Faculte de Medecine
|
|
Pitie-Salpetriere, Paris, France. The effects of the 5-HT3 receptor antagonists, zacopride, ondansetron and
|
|
ICS 205-930, were investigated in an animal model of depression, the learned helplessness test. Rats
|
|
previously subjected to a session of 60 inescapable foot-shocks exhibited a deficit of escape performance in
|
|
three subsequent shuttle-box sessions. The 5-HT3 receptor antagonists administered i.p. twice daily on a
|
|
chronic schedule (zacopride 0.03-2 mg/kg per day; ondansetron and ICS 205-930: 0.125-2 mg/kg per day)
|
|
reduced the number of escape failures at low to moderate daily doses. This effect was not observed with the
|
|
highest dose(s) of zacopride, ondansetron and ICS 205-930 tested.. These results indicate that 5-HT3
|
|
antagonists may have effects like those of conventional antidepressants in rats.
|
|
</p>
|
|
<p>
|
|
Neuropharmacology 1992 Apr;31(4):323-30. <strong>Presynaptic serotonin mechanisms in rats subjected to
|
|
inescapable shock.</strong> Edwards E, Kornrich W, Houtten PV, Henn FA. "After exposure to
|
|
uncontrollable shock training, two distinct groups of rats can be defined in terms of their performance in
|
|
learning to escape from a controllable stress. Learned helpless rats do not learn to terminate the
|
|
controllable stress, whereas non-learned helpless rats learn this response as readily as naive control rats
|
|
do." "These results implicate presynaptic serotonin mechanisms in the behavioral deficit caused by
|
|
uncontrollable shock. In addition, a limbic-hypothalamic pathway may serve as a control center for the
|
|
behavioral response to stress."
|
|
</p>
|
|
<p>
|
|
Neurochem Int 1992 Jul;21(1):29-35.<strong>
|
|
In vitro neurotransmitter release in an animal model of depression</strong>. Edwards E, Kornrich W, van
|
|
Houtten P, Henn FA. "Sprague-Dawley rats exposed to uncontrollable shock can be separated by a subsequent
|
|
shock escape test into two groups: a "helpless" (LH) group which demonstrates a deficit in escape behavior,
|
|
and a "nonlearned helpless" (NLH) group which shows no escape deficit and acquires the escape response as
|
|
readily as naive control rats (NC) do." "The major finding concerned a significant increase in endogenous
|
|
and K(+)-stimulated serotonin (5-HT) release in the hippocampal slices of LH rats. There were no apparent
|
|
differences in acetylcholine, dopamine and noradrenaline release in the hippocampus of LH rats as compared
|
|
to NLH and NC rats. These results add further support to previous studies in our laboratory which implicate
|
|
presynaptic 5-HT mechanisms in the behavioral deficit caused by uncontrollable shock."
|
|
</p>
|
|
<p>
|
|
Psychiatry Res 1994 Jun;52(3):285-93. <strong>In vivo serotonin release and learned helplessness.</strong>
|
|
Petty F, Kramer G, Wilson L, Jordan S Mental Health Clinic, Dallas Veterans Affairs Medical Center, TX.
|
|
Learned helplessness, a behavioral depression caused by exposure to inescapable stress, is considered to be
|
|
an animal model of human depressive disorder. Like human depression, learned helplessness has been
|
|
associated with a defect in serotonergic function, but the nature of this relationship is not entirely
|
|
clear. We have used in vivo microdialysis brain perfusion to measure serotonin (5-hydroxytryptamine, 5HT) in
|
|
extracellular space of medial frontal cortex in conscious, freely moving rats. Basal 5HT levels in rats
|
|
perfused before exposure to tail-shock stress did not themselves correlate with subsequent learned
|
|
helplessness behavior. However, 5HT release after stress showed a significant increase with helpless
|
|
behavior. <strong>These data support the hypothesis that a cortical serotonergic excess is causally related
|
|
to the development of learned helplessness.</strong>
|
|
</p>
|
|
<p>
|
|
Pharmacol Biochem Behav 1994 Jul;48(3):671-6. <strong>Does learned helplessness induction by haloperidol
|
|
involve serotonin mediation?</strong> Petty F, Kramer G, Moeller M Veterans Affairs Medical Center,
|
|
Dallas 75216. Learned helplessness (LH) is a behavioral depression following inescapable stress. Helpless
|
|
behavior was induced in naive rats by the dopamine D2 receptor blocker haloperidol (HDL) in a dose-dependent
|
|
manner, with the greatest effects seen at 20 mg/kg (IP). Rats were tested 24 h after injection. Haloperidol
|
|
(IP) increased release of serotonin (5-HT) in medial prefrontal cortex (MPC) as measured by in vivo
|
|
microdialysis. Perfusion of HDL through the probe in MPC caused increased cortical 5-HT release, as did
|
|
perfusion of both dopamine and the dopamine agonist apomorphine. Our previous work found that increased 5-HT
|
|
release in MPC correlates with the development of LH. The present work suggests that increased DA release in
|
|
MPC, known to occur with both inescapable stress and with HDL, may play a necessary but not sufficient role
|
|
in the development of LH. Also, this suggests that increased DA activity in MPC leads to increased 5-HT
|
|
release in MPC and to subsequent behavioral depression.
|
|
</p>
|
|
<p>
|
|
Arzneimittelforschung 1975 Nov; 25(11):1737-44<strong>. [Central action of WA-335-BS, a substance with
|
|
peripheral antiserotonin and antihistaminic activity].</strong> Kahling J, Ziegler H, Ballhause H. "In
|
|
rats and mice the serotonin and histamine antagonistic drug <strong>. . .</strong> (WA 335-BS) caused
|
|
stronger central sedative effects than did cyproheptadine. WA 335-BS also displayed stronger activity
|
|
against reserpine- and central tremorine-induced effects than did cyproheptadine and it slightly enhanced
|
|
d-amphetamine-induced<strong> </strong>
|
|
|
|
effects:<strong>
|
|
therefore it may have antidepressant properties. WA 335-BS proved to be</strong>
|
|
<strong>very effective against isolation-induced aggression in male mice.</strong> The comparatively small
|
|
anxiolytic effects may have been caused in part by the central antiserotonin properties." "The results of
|
|
our animal studies suggest WA 335-BS to be an antidepressant with sedative properties."
|
|
</p>
|
|
<p>
|
|
Neuroscience 2000;100(4):749-68<strong>. Behavioral, neurochemical and endocrinological characterization of
|
|
the early social isolation syndrome.</strong> Heidbreder CA, Weiss IC, Domeney AM, Pryce C, Homberg J,
|
|
Hedou G, Feldon J, Moran MC, Nelson P. "Rearing rats in isolation has been shown to be a relevant paradigm
|
|
for studying early life stress and<strong>
|
|
understanding the genesis of depression and related affective disorders.</strong> Recent studies from
|
|
our laboratory point to the relevance of studying the social isolation syndrome as a function of home caging
|
|
conditions."
|
|
</p>
|
|
|
|
<p>
|
|
Stroke 1991 Nov;22(11):1448-51. <strong>Platelet secretory products may contribute to neuronal
|
|
injury.</strong> Joseph R, Tsering C, Grunfeld S, Welch KM. BACKGROUND: We do not fully understand the
|
|
mechanisms for neuronal damage following cerebral arterial occlusion by a thrombus that consists mainly of
|
|
platelets. The view that certain endogenous substances, such as glutamate, may also contribute to neuronal
|
|
injury is now reasonably well established. Blood platelets are known to contain and secrete a number of
|
|
substances that have been associated with neuronal dysfunction. Therefore, we hypothesize that a high
|
|
concentration (approximately several thousand-fold higher than in plasma, in our estimation) of locally
|
|
released platelet secretory products derived from the causative thrombus may contribute to neuronal injury
|
|
and promote reactive gliosis. SUMMARY OF COMMENT: We have recently been able to report some direct support
|
|
for this concept. When organotypic spinal cord cultures were exposed to platelet and platelet products, a
|
|
significant reduction in the number and the size of the surviving neurons occurred in comparison with those
|
|
in controls. We further observed that serotonin, a major platelet product, has neurotoxic properties. There
|
|
may be other platelet components with similar effect.<strong>
|
|
CONCLUSIONS: The hypothesis of platelet-mediated neurotoxicity gains some support from these recent in
|
|
vitro findings. The concept could provide a new area of research in stroke, both at the clinical and
|
|
basic levels.</strong>
|
|
</p>
|
|
<p>
|
|
Am J Psychiatry 1981 Aug;138(8):1082-5.<strong>
|
|
Tryptophan metabolism in children with attentional deficit disorder.</strong> Irwin M, Belendiuk K,
|
|
McCloskey K, Freedman DX The authors present the first report, to their knowledge, of hyperserotonemia in
|
|
children with attentional deficit disorder who had normal intelligence. Hyperserotonemic children had
|
|
significantly lower levels of plasma total and protein-bound tryptophan and a higher percentage of free
|
|
tryptophan than those with normal serotonin levels. Plasma kynurenine did not differ, suggesting that the
|
|
hyperserotonemia is not due to a blockade of the kynurenine pathway but may reflect on increase in tissue
|
|
tryptophan uptake and use.
|
|
</p>
|
|
<p>
|
|
J Neuropsychiatry Clin Neurosci 1990 Summer;2(3):268-74.<strong>
|
|
Autistic children and their first-degree relatives: relationships between serotonin and norepinephrine
|
|
levels and intelligence.</strong> Cook EH, Leventhal BL, Heller W, Metz J, Wainwright M, Freedman DX
|
|
"Whole-blood serotonin (5-HT) and plasma norepinephrine (NE) were studied in 16 autistic children, 21
|
|
siblings of autistic children, and 53 parents of autistic children. <strong>Both plasma NE and whole-blood
|
|
5-HT were negatively correlated with vocabulary performance."
|
|
</strong>
|
|
|
|
"Eighteen subjects were hyperserotonemic (whole-blood 5-HT greater than 270 ng/ml). For these subjects,
|
|
plasma NE was significantly higher than for subjects without hyperserotonemia."
|
|
</p>
|
|
<p>
|
|
Biol Psychiatry 1998 Dec 15;44(12):1321-8. <strong>Cerebrospinal fluid monoamines in Prader-Willi
|
|
syndrome.</strong> Akefeldt A, Ekman R, Gillberg C, Mansson JE "The behavioral phenotype of Prader-Willi
|
|
syndrome (PWS) suggests hypothalamic dysfunction and altered neurotransmitter regulation. The purpose of
|
|
this study was to examine whether there was any difference in the concentrations of monoamine metabolites in
|
|
the cerebrospinal fluid (CSF) in PWS and non-PWS comparison cases." "The concentrations of<strong>
|
|
dopamine and particularly serotonin metabolites were increased in the PWS group. The differences were
|
|
most prominent for 5-hydroxyindoleacetic acid. The increased concentrations were found in all PWS cases
|
|
independently of age, body mass index, and level of mental retardation." "The findings implicate
|
|
dysfunction of the serotonergic system and possibly also of the dopamine system
|
|
</strong>
|
|
in PWS individuals . . . ."
|
|
</p>
|
|
<p>
|
|
Pharmacol Biochem Behav 1976 Jul;5(1):55-61. <strong>The role of serotonergic pathways in isolation-induced
|
|
aggression in mice.</strong> Malick JB, Barnett A Male mice that became aggressive following four weeks
|
|
of social isolation were treated with seven known serotonin receptor antagonists. All of the<strong>
|
|
antiserotonergic drugs selectively antagonized the fighting behavior of the isolated mice; the
|
|
antiaggressive activity was selective since, at antifighting doses, none of the drugs either
|
|
significantly altered spontaneous motor activity</strong>
|
|
|
|
or impaired inclined-screen performance. <strong>Antagonism of 5-HTP-induced head-twitch was used as an in
|
|
vivo measure of antiserotonergic activity and a statistically significant correlation existed between
|
|
potency as an antiserotonergic and potency as an antiaggressive.</strong> PCPA, a serotonin depletor,
|
|
also significantly <strong>antagonized isolation-induced aggression</strong> for at least 24 hr postdrug
|
|
administration. The interrelationship between cholinergic and serotonergic mechanisms in the mediation of
|
|
isolation aggression was investigated. The involvement of serotonergic systems in isolation-induced
|
|
aggression is discussed.
|
|
</p>
|
|
<p>
|
|
Probl Endokrinol (Mosk) 1979 May-Jun;25(3):49-52<strong>
|
|
[Role of serotonin receptors of the medial-basal hypothalamus in the mechanisms of negative feedback of
|
|
the hypophyseal-testicular complex].</strong> Naumenko EV, Shishkina GT. "Administration of serotonin
|
|
into the lateral ventricle of the brain of male rats, against the background of complete isolation of the
|
|
medial-basal hypothalamus was accompanied by the block of the compensatory elevation of the blood
|
|
testosterone level following unilateral castration."
|
|
</p>
|
|
<p>
|
|
Encephale 1994 Sep-Oct;20(5):521-5. <strong>[Can a serotonin uptake agonist be an authentic antidepressant?
|
|
Results of a multicenter, multinational therapeutic trial].</strong> Kamoun A, Delalleau B, Ozun M The
|
|
classical biochemical hypothesis of depression posits a functional deficit in central neurotransmitter
|
|
systems particularly serotonin (5-HT) and noradrenaline. The major role suggested for 5-HT in this theory
|
|
led to the development of a large number of compounds which selectively inhibit 5-HT uptake. Numerous
|
|
clinical trials have demonstrated the antidepressant efficacy of such types of serotoninergic agents,
|
|
supporting 5-HT deficit as the main origin of depression. <strong>Therefore, everything seemed clear:
|
|
depression was caused by 5-HT deficit. Tianeptine is clearly active in classical animal models
|
|
predictive of antidepressant activity, and is also active in behavioral screening tests: it antagonizes
|
|
isolation induced aggression in mice and behavioral despair in rats.</strong> Biochemical studies have
|
|
revealed that in contrast to classical tricyclic antidepressant,<strong>
|
|
tianeptine stimulates 5-HT uptake
|
|
</strong>
|
|
in vivo in the rat brain. This somewhat surprising property was observed in the cortex and the hippocampus
|
|
following both acute and chronic administrations. This increase in 5-HT uptake has also been confirmed in
|
|
rat platelets after acute and<strong>
|
|
chronic administrations. Moreover, in humans, a study in depressed patients demonstrated that tianeptine
|
|
significantly increased platelet 5-HT uptake after a single administration as well as after 10 and 28
|
|
days of treatment. The antidepressant activity of tianeptine has been evaluated in controlled studies
|
|
versus reference antidepressants. Another study aiming to compare the antidepressant efficacy of
|
|
tianeptine versus placebo and versus imiporamine is</strong> presented. 186 depressed patients were
|
|
included in this trial. They presented with either Major Depression, single episode (24.6%) or Major
|
|
Depression recurrent (66.8%) or Bipolar Disorder (depressed) (8.6%).
|
|
</p>
|
|
<p>
|
|
Psychopharmacology (Berl) 1998 Oct;139(3):255-60.<strong>
|
|
Ca2+ dependency of serotonin and dopamine release from CNS slices of chronically isolated rats.</strong>
|
|
Jaffe EH. "We have used chronic isolated housing as an animal model of depression." "The following questions
|
|
were addressed: first, if there is a change in the depolarization dependent release of DA and 5-HT from
|
|
these CNS structures, and second, if the release is through the classical exocytotic mechanism. <strong>A
|
|
significant increase in KCl stimulated release of 5-HT was observed in chronically isolated animals when
|
|
compared to controls.
|
|
</strong>
|
|
5-HT release was completely abolished from controls or isolated animals, when slices were incubated with
|
|
Krebs containing zero Ca2+/10 mM Mg2+, the inorganic Ca2+ channel blockers, Cd2+ or Ni2+ and the calmodulin
|
|
inhibitor, trifluoperazine." <strong>"The basal release of DA and 5-HT was similar in control and isolated
|
|
animals and was not affected by the Ca2+ channel antagonists. The results suggest that extracellular
|
|
Ca2+-dependent release of 5-HT and, to a lesser degree, of DA, is increased in this chronic animal model
|
|
of depression in</strong> several CNS structures."
|
|
</p>
|
|
|
|
<p>
|
|
Gen Pharmacol 1994 Oct;25(6):1257-1262.<strong>
|
|
Serotonin-induced decrease in brain ATP, stimulation of brain anaerobic glycolysis and elevation of
|
|
plasma hemoglobin; the protective action of calmodulin antagonists.</strong> Koren-Schwartzer N,
|
|
Chen-Zion M, Ben-Porat H, Beitner R Department of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
|
|
<strong>1. Injection of serotonin (5-hydroxytryptamine) to rats, induced a dramatic fall in brain ATP level,
|
|
accompanied by an increase in P(i). Concomitant to these changes, the activity of cytosolic
|
|
phosphofructokinase, the rate-limiting enzyme of glycolysis, was significantly enhanced. Stimulation of
|
|
anaerobic glycolysis was also reflected by a marked increase in lactate content in brain. 2. Brain
|
|
glucose</strong> 1,6-bisphosphate level was decreased, whereas fructose 2,6-bisphosphate was unaffected
|
|
by serotonin. 3. All these serotonin-induced changes in brain, which are characteristic for cerebral
|
|
ischemia, were prevented by treatment with the calmodulin (CaM) antagonists, trifluoperazine or
|
|
thioridazine. 4<strong>.. Injection of serotonin also induced a marked elevation of plasma hemoglobin,
|
|
reflecting lysed erythrocytes,</strong> which was also prevented by treatment with the CaM antagonists.
|
|
5.<strong>
|
|
The present results suggest that CaM antagonists may be effective drugs in treatment of many
|
|
pathological conditions and diseases in which plasma serotonin levels are known to increase.</strong>
|
|
</p>
|
|
<p>
|
|
Gen Pharmacol 1994 Oct;25(6):1257-1262.<strong>
|
|
Serotonin-induced decrease in brain ATP, stimulation of brain anaerobic glycolysis and elevation of
|
|
plasma hemoglobin; the protective action of calmodulin antagonists.</strong> Koren-Schwartzer N,
|
|
Chen-Zion M, Ben-Porat H, Beitner R Department of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
|
|
<strong>1. Injection of serotonin (5-hydroxytryptamine) to rats, induced a dramatic fall in brain ATP level,
|
|
accompanied by an increase in P(i). Concomitant to these changes, the activity of cytosolic
|
|
phosphofructokinase, the rate-limiting enzyme of glycolysis, was significantly enhanced. Stimulation of
|
|
anaerobic glycolysis was also reflected by a marked increase in lactate content in brain. 2. Brain
|
|
glucose</strong> 1,6-bisphosphate level was decreased, whereas fructose 2,6-bisphosphate was unaffected
|
|
by serotonin. 3. All these serotonin-induced changes in brain, which are characteristic for cerebral
|
|
ischemia, were prevented by treatment with the calmodulin (CaM) antagonists, trifluoperazine or
|
|
thioridazine. 4. Injection of serotonin also induced a marked elevation of plasma hemoglobin, reflecting
|
|
lysed erythrocytes, which was also prevented by treatment with the CaM antagonists. 5. The present results
|
|
suggest that CaM antagonists may be effective drugs in treatment of many pathological conditions and
|
|
diseases in which plasma serotonin levels are known to increase.
|
|
</p>
|
|
|
|
<p>
|
|
J Neural Transm 1998;105(8-9):975-86. <strong>Role of tryptophan in the elevated serotonin-turnover in
|
|
hepatic encephalopathy.</strong> Herneth AM, Steindl P, Ferenci P, Roth E, Hortnagl H. "The increase of
|
|
the brain levels of 5-hydroxyindoleacetic acid (5-HIAA) in hepatic encephalopathy (HE) suggests an increased
|
|
turnover of serotonin (5-HT)." "These results provide further evidence for the role of tryptophan in the
|
|
elevation of brain 5-HT metabolism and for a potential role of BCAA in the treatment of HE."
|
|
</p>
|
|
<p>
|
|
Tugai VA; Kurs'kii MD; Fedoriv OM. <strong>[Effect of serotonin on Ca2+ transport in mitochondria conjugated
|
|
with the respiratory chain].</strong> Ukrainskii Biokhimicheskii Zhurnal, 1973 Jul-Aug, 45(4):408-12.
|
|
</p>
|
|
<p>
|
|
Kurskii MD; Tugai VA; Fedoriv AN.<strong>
|
|
[Effect of serotonin and calcium on separate components of respiratory chain of mitochondria in some
|
|
rabbit tissues].</strong>
|
|
Ukrainskii Biokhimicheskii Zhurnal, 1970, 42(5):584-8.
|
|
</p>
|
|
|
|
<p>
|
|
Watanabe Y; Shibata S; Kobayashi B. <strong>Serotonin-induced swelling of rat liver mitochondria.</strong>
|
|
Endocrinologia Japonica, 1969 Feb, 16(1):133-47.
|
|
</p>
|
|
<p>
|
|
Mahler DJ; Humoller FL. <strong>The influence of serotonin on oxidative metabolism of brain
|
|
mitochondria.</strong> Proceedings of the Society for Experimental Biology and Medicine, 1968 Apr,
|
|
127(4):1074-9.
|
|
</p>
|
|
<p>
|
|
Eur J Pharmacol 1994 Aug 11;261(1-2):25-32. <strong>The effect of alpha 2-adrenoceptor antagonists in
|
|
isolated globally ischemic rat hearts.</strong> Sargent CA, Dzwonczyk S, Grover G.J. "The alpha
|
|
2-adrenoceptor antagonist, yohimbine, has been reported to protect hypoxic myocardium. Yohimbine has several
|
|
other activities, including 5-HT receptor antagonism, at the concentrations at which protection was found."
|
|
"Pretreatment with yohimbine (1-10 microM) caused a concentration-dependent increase in reperfusion left
|
|
ventricular developed pressure and a reduction in end diastolic pressure and lactate dehydrogenase release.
|
|
The structurally similar compound rauwolscine (10 microM) also protected the ischemic myocardium. In
|
|
contrast, idozoxan (0.3-10 microM) or tolazoline (10 microM) had no protective effects. The<strong>
|
|
cardioprotective effects of yohimbine were partially reversed by 30 microM 5-HT. These results indicate
|
|
that the mechanism for the cardioprotective activity of yohimbine may involve 5-HT receptor antagonistic
|
|
activity."
|
|
</strong>
|
|
</p>
|
|
|
|
<p>
|
|
Zubovskaia AM. <strong>[Effect of serotonin on some pathways of oxidative metabolism in the mitochondria of
|
|
rabbit heart muscle].</strong> Voprosy Meditsinskoi Khimii, 1968 Mar-Apr, 14(2):152-7.
|
|
</p>
|
|
<p>
|
|
Warashina Y. <strong>
|
|
[On the effect of serotonin on phosphorylation of rat liver mitochondria</strong>]. Hoppe-Seylers
|
|
Zeitschrift fur Physiologische Chemie, 1967 Feb, 348(2):139-48.
|
|
</p>
|
|
<p>
|
|
Eur Neuropsychopharmacol 1997 Oct;7 Suppl 3:S323-S328. <strong>Prevention of stress-induced morphological
|
|
and cognitive consequences</strong>.. McEwen BS, Conrad CD, Kuroda Y, Frankfurt M, Magarinos AM,
|
|
McKittrick C. Atrophy and dysfunction of the human hippocampus is a feature of aging in some individuals,
|
|
and this dysfunction predicts later dementia. There is reason to believe that adrenal glucocorticoids may
|
|
contribute to these changes, since the elevations of glucocorticoids in Cushing's syndrome and during normal
|
|
aging are associated with atrophy of the entire hippocampal formation in humans and are linked to deficits
|
|
in short-term verbal memory. We have developed a model of stress-induced atrophy of the hippocampus of rats
|
|
at the cellular level, and we have been investigating underlying mechanisms in search of agents that will
|
|
block the atrophy. Repeated restraint stress in rats for 3 weeks causes changes in the hippocampal formation
|
|
that include suppression of 5-HT1A receptor binding and atrophy of dendrites of CA3 pyramidal neurons, as
|
|
well as impairment of initial learning of a radial arm maze task. <strong>
|
|
Because serotonin is released by stressors and may play a role in the actions of stress on nerve cells,
|
|
we investigated the actions of agents that facilitate or inhibit serotonin reuptake.</strong> Tianeptine
|
|
is known to enhance serotonin uptake, and we compared it with fluoxetine, an inhibitor of 5-HT reuptake, as
|
|
well as with desipramine. <strong>Tianeptine treatment (10 mg/kg/day) prevented the stress-induced atrophy
|
|
of dendrites of CA3 pycamidal neurons,</strong> whereas neither fluoxetine (10 mg/kg/day) nor
|
|
desipramine (10 mg/kg/day) had any effect. <strong>Tianeptine treatment also prevented the stress-induced
|
|
impairment of radial maze learning.</strong>
|
|
|
|
Because <strong>corticosterone- and stress-induced atrophy of CA3 dendrites is also blocked by phenytoin, an
|
|
inhibitor of excitatory amino acid release and actions, these results suggest that serotonin released by
|
|
stress or corticosterone may interact pre- or post-synaptically with glutamate released by stress or
|
|
corticosterone, and that the final common path may involve interactive effects between serotonin and
|
|
glutamate receptors on the dendrites of CA3 neurons innervated by mossy fibers from the dentate gyrus.
|
|
We discuss the implications of these findings for treating cognitive impairments and the risk for
|
|
dementia in the elderly.</strong>
|
|
</p>
|
|
|
|
© Ray Peat Ph.D. 2009. All Rights Reserved. www.RayPeat.com
|
|
</body>
|
|
</html>
|