Dopamine
LN...@wombat.newcastle.edu.au
private email from a postgrad. neurobiologist friend of mine at Penn.
Uni. (Mickey Rowe). I had been checking some of my theories of the possible
causes of my hypersensitivity and other symptoms with him and then came this
(partially reproduced) response. The quotations are from the book by Kuffler,
Nicholls and Martin: "From Neuron To Brain".
---------cut here-------------------
......(Interesting stuff about allergies and anaemia deleted)......
>I think that your basic idea is very good, though. Proteins mistaking
>foreign substances for the molecules that really belong there does
>happen, and may be part of the syndromes you're trying to
>characterize.
>
>>2. Norepinephrine; Dopamine and 5-HT are secreted in very
>>discrete regions of the brain and diffuse along set pathways to all
>>other regions. Norepinephrine is also released by nerves in internal
>>organs, including gut, spleen and heart (and adrenal glands?).
(*Here I'm looking for an explanation of my physical reactions to stress -
possibly caused by excess norepinephrine in my system?)
>If I recall correctly, adrenal cortex secretes primarily epinephrine,
>but the adrenal medulla does secrete norepinephrine.
>
>This is probably just my bias (since I'm not a pharmacologist), but I
>tend to take the subject of these pathways with large grains of salt.
>People always want to make things simpler than they really are, and
>one of the ideas that popped out of some of the early work in
>neuropharmacology was that you could characterize "circuits" based on
>the neurotransmitters that they secreted. However, we now know that
>many (most ?) cells respond to more than one type of transmitter, and
>some probably release more than one type. While there are probably
>populations of cells that project axons together and use primarily the
>same transmitter on their target cells, I suspect that the details of
>the wiring are more important than these gross features.
>
>On the other hand, Tourette's syndrome, autism and schizophrenia seem
>to argue against me. I think that too much Dopamine seems to go along
>with the first and third, and too little dopamine with autism. You
>might be curious to look into these diseases to find out more of the
>current thinking here. A guy named David Lewis was just here talking
>about dopamine circuitry in the frontal lobes of humans, specifically
>because he's interested in the ontogeny of schizophrenia. I'm afraid
>that I wasn't as attuned to him as I was with the guy from St.
>Petersburg, or I'd try to tell you more about his talk.
...............(Remainder deleted)
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At the time I wasn't paying too much attention to autism and accepted his
reference on the basis that he knew what he was talking about. I continued
reading the latest publications relating to brain chemistry (for fun?). In
one of these books (I think it was: BRADSHAW, John L. Hemispheric
Specialization and Psychological Function. John Wiley & Sons. Chichester. 1989.
but if it's not then it most certainly is in one of these:
IWAI, Eiichi & MISHKIN, Mortimer (Eds.) Vision, Memory and the Temporal Lobe.
Elsevier, New York. 1990.
MASON, Stephen T. Catecholamines and Behaviour. C.U.P.
Cambridge. 1984.
BASSUK, Ellen & SCHOONOVER, Stephen C. The Practitioner's Guide to
Psychoactive Drugs. Plenum. New York. 1977.
HARPER, A. Murray & JENNETT, Sheila (Eds.) Cerebral blood flow and
metabolism. Manchester U. P. Manchester. 1990.)
I found a research reference linking autism to lack of dopamine in the brain.
I am unable to check this out at the moment, as these books have now been
returned to the library and are now on loan to another Ph.D. student.
Springer & Deutsch (Left Brain, Right Brain. 3rd Ed.) cite references to
research that supports the link between autism and hemispheric asymmetry...
but some unexplained symptoms that are purported to involve the right-
hemisphere seem to deny this. I therefore postulated that the problem could
lie in the dopaminergic system.....if for some reason insufficient quantities
of dopamine were being produced to allow the brain to function adequately -
some of these sites are in the right hemisphere and therefore malfunctions
would not be confined to the left, explaining the discrepancies. The benefits
reported to be derived from the use of Ritalin and other 'dopamine-producing'
drugs, including alcohol (I have always wondered why I became abnormally
fluent after a few brandys and I have observed that my children and I also
experience increases in fluency when we experience 'indignant outrage'), seem
to support this theory.
To answer Bob's question: L-Dopa doesn't work....it's been tried, but Bradshaw
(I think) states that L-Dopa is the basic building block for both dopamine
and norepinephrine. It is the presence of particular enzymes that determine
which neurotransmitter is produced. I have a feeling that it is the dopamine-
producing enzyme that we have in insufficient quantities. This is speculation
on my part (Mickey tells me that neurobiology is 20 years behind where I would
like it to be), but so far the pieces of the puzzle seem to be falling into
place......I just have to wait now until medical science confirms or denies
my beliefs.
Carolyn
D...@sjuvm.bitnet
up with two references that related a subtype of Autism to elevated
Serotonin levels in the brain (Geller et al, New England Journal of
Medicine, 1982; Ritvo, et al, Journal of the American Academy of
Child Psychiatry, 1983). I have not yet checked these references, but
I will and I plan a search on Autism and biochem and neuropsych.
Thanx for the push, Carolyln.
I also looked at the Springer and Deutsch, and while they do report evidence
of Left Hemispere involvement with Autism, they include opposing arguments
and suggest that hemispheric involvement in autism be examined on a case
by case basis. That is one of the reasons that I asked for information
on gaze shift and directional preferrences of autistic children. Are
there subtypes of autism related to lack of dopamine on one hand and
an excess of serotonin on the other?
Bob Zenhausern, Ph.D.
St. John's University Bitnet: d...@sjuvm.bitnet
SB 15 Marillac Phone: 718-990-6447
Jamaica, NY 11439 Fax: 718-990-6705
LN...@wombat.newcastle.edu.au
Thanks for the references - I'll check them out the next time I'm at the
library. I hadn't heard of subtypes of autism (although I had suspected it)
before - seems to make sense to me. Most of my problems seem to be related
to excess 'adrenalin' levels (that is when I am excited or under stress).
I wonder if I am a 'norepinephrenic subtype'? Although when I am depressed
I have trouble staying awake and lose the ability to feel pain. Now, I know
that serotonin is reported to be responsible for this, but I can't find a
reference to tell me if it is due to an excess or lack of it. If it is
excess then is it possible that both the norepinephrinergic and serotonergic
systems have 'over-developed' due to the underdevelopment of the dopaminergic
system? If so, then it seems to me that the subtype would be determined by
the 'mood' and/or personality type of the individual rather than there being
any specific subtype involved.
I interpreted the arguments in Springer & Deutsch as being against 'cerebral
dominance' theories. I am not advocating that people are either 'right-brained'
or 'left-brained', but after reading that dopamine and norepinephrine were
considered to be major transmitters in the left and right hemispheres
respectively, it occurred to me that an alternative explanation would be that
many of the functions that were normally handle by the dopaminergic system may
have been adapted to be served by the norepinephrenic system in autistics.
Kuffler et al claim that norepinephrine can activate some dopaminergic sites
although not to the same degree of efficiency as dopamine. The reported lack
of asymmetry in LD's (and women?) seems to fit in here also. Is my thinking
TOO autistic here?
Carolyn
Jim Sinclair
Ritvo & Freeman did lots of studies on the serotonin connection during
the mid- to late 1980s. There was some excitement about the use of
fenfluramine, which did lower serotonin levels in some autistic children
but usually didn't have much effect on autistic behavior. I think this
is just another way to identify subtypes of autism, not a central
defining feature of autism.
JS
D...@sjuvm.bitnet
Neurochemistry is not one of my strong points, but it is my understanding
that L-dopa is a precoursor of Dopamine which is a precursor of
epinepheron and nor-epinepheron and all belong to the catacholomines.
I have seen some evidence that the catecholamines are more left hemisphere
oriented (I think it was Saucy in Science, 1982) but not enough to
a bet on. I have drawn paralles between these adrenergic neurotransmitters
and the symapthetic system. Serotonin on the other hand, I have always
assoicated with the right hemisphere, cholinergic neurotransmitters, and
the parasympathetic system. If there are any better informed on the List
I would appreciate the clarification of errors in thinking or memory.
If my reasoning is correct, it is possible that a deficit in dopamine
in the Left Hemisphere could be related to an excess of serotonin
in the Right Hemisphere. Or both could vary independently leaving
the possiblity of 4 biochemically distinct subtypes of autism.
In terms of thinking strategies, Carolyn, you described yourself as
perceiving the world wholistically and deducing the reality of your
perceptions on a trial and error basis. I take this to mean that
you are using the processing strategies that are typically associated
with the Right Hemisphere. Jim Sinclair has frequently described
himself as using Left Hemisphere thinking strategies and IMO
his experiences feel different from yours. This does not have to
mean that there are Right and Left Autistics. Maybe, both Right and Left
individuals can be autistic and maybe the strategies we use to deal with
autistic symptoms need to match learning styles.
LN...@wombat.newcastle.edu.au
I'm no neurochemist either - just a linguistics post-grad. - I have to get all
this stuff out of books that I'm not sure I have the background to understand
properly, but I can give you the quotes that led me say what I said.
The one about L-Dopa being converted to both dopamine and norepinephrine
by two different enzymes came from the Bradshaw reference (which I don't
have now). It gave the names of the particular enzymes involved (I tried to
commit them to memory but it failed).
Springer & Deutsch (pp.136) state: "There is some speculation that the extra
norepinephrine defined pathways of the right hemisphere complement the extra
dopamine defined pathways of the left in terms of attentional mechanisms they
subserve, which, in turn, lead to some of the well documented hemispheric
asymmetries in function..." and they later refer to these two as major
neurotransmitters in their respective hemispheres.
Kuffler et al (a more reliable source I think) says:-
"Within the mammalian nervous system, there is evidence that norepinephrine,
epinephrine, dopamine, and 5-hydroxytryptamine act as transmitters. They are
found in pathways essential for sensory and motor performance as well as for
higher functions. However, out of the total cells in the human brain,
relatively few appear to contain these transmitters - thousands rather than
millions or billions. What is more, most of the cells containing one of
these transmitters are clustered together in a discrete region of the brain.
Thus, in the rat central nervous system the majority of cells containing
norepinephrine - only about one thousand five hundred or so in number - are
located in a small nucleus known as the _locus coeruleus_. Those for dopamine
lie for the most part in the _substantia nigra_, and those for 5-hydroxytryp-
tamine in groups of cells called _raphe nuclei_. From these areas,....., fibers
spread out to supply virtually all areas of the brain. For example,
norepinephrine fibers supply the cerebellar Purkinje cells, the cerebral
cortex, and the thalamus. A single cell can branch to supply structures to
supply widely different areas. Dopamine-containing fibers supply structures
such as the basal ganglia in addition to the cortex. 5-Hydroxytryptamine
-containing fibers are almost ubiquitous."
>If my reasoning is correct, it is possible that a deficit in dopamine
>in the Left Hemisphere could be related to an excess of serotonin
>in the Right Hemisphere. Or both could vary independently leaving
>the possiblity of 4 biochemically distinct subtypes of autism.
What Kuffler et al said above would seem to indicate that the effects of
excess serotonin (5-hydroxtryptamine) would be even more pervasive. Is it
possible that the excess serotonin gives us our characteristic autistic
behaviour, but in my case I have excess norepinephrine as well and Jim
has excess dopamine levels? Could this explain the differences?
>In terms of thinking strategies, Carolyn, you described yourself as
>perceiving the world wholistically and deducing the reality of your
>perceptions on a trial and error basis. I take this to mean that
>you are using the processing strategies that are typically associated
>with the Right Hemisphere. Jim Sinclair has frequently described
>himself as using Left Hemisphere thinking strategies and IMO
>his experiences feel different from yours. This does not have to
>mean that there are Right and Left Autistics. Maybe, both Right and Left
>individuals can be autistic and maybe the strategies we use to deal with
>autistic symptoms need to match learning styles.
Could it be that excess norepinephrine or excess dopamine determine the
learning style and excess serotonin the autism?
Carolyn