Fw: "Opioid receptors, addiction and beyond" Lecture at Rockefeller University by Brigitte Kieffer.

Preston Peet ptpeet at nyc.rr.com
Wed Jun 14 12:57:14 EDT 2006


----- Original Message ----- 
From: Andrew Byrne
To: ajbyrne at ozemail.com.au
Sent: Wednesday, June 14, 2006 2:00 AM
Subject: "Opioid receptors, addiction and beyond" Lecture at Rockefeller 
University by Brigitte Kieffer.


"Opioid receptors, addiction and beyond "

Professor Brigitte Kieffer, Ph.D.
Institut de Génétique et de Biologie Moléculaire et Cellulaire
CNRS/INSERM/ULP, Université de Strasbourg, France

Inter-Institutional Narcotic and Ethanol Group Lecture
1:00pm Tuesday, May 2, 2006 - Caspary Hall 1B, Rockefeller University, York 
Avenue, NYC.

Dear Colleagues,
In little over an hour, this informative presentation brought us up to date 
on the state of the art regarding cloned opioid receptors, rat experiments, 
fluorescent antibodies and cellular changes associated with opioids. 
Clinically in opioid addiction, these involve: initiation, maintenance, 
dependency, habituation, withdrawal, abstinence and relapse to drug use.

Dr Kieffer started with the simplest description of drug use and the 
inevitable brain changes which occur with tolerance at the receptor level. 
As she pointed out, all of the consequences of drug use are mediated by such 
receptors and can be understood in terms of old pharmacology research with 
corroboration from more recent work on the defined receptors themselves.  Dr 
Kieffer's group in Strasbourg was the first to clone the opioid receptor, 
which was also done independently at the same time by Evans' group in 
California.

We were told about behavioural experiments in mice cloned to have one, two 
or three gene "knock-outs" being mu, kappa or delta opioid receptors.  The 
first and most important finding was that such animals (even triple 
'knock-outs') are still viable, proving that (some) mammals do not require 
the opioid system for survival and procreation.

Such receptors were predicted long before they were specifically isolated 
and such rats were bred in the late 1980s.  The experiments with mu 
receptors were all completely predictable based on previous pharmacology but 
this was not the case with delta or kappa receptors.  To examine analgesic 
and euphoric effects, they used tests of self administration ('press the 
lever'), tail immersion, dark room, bright lights, place preference, 
preferred routes, maternal smell recognition and a number of other 
interesting tests on the cloned and 'wild type' rodents.  Consistent with 
some of the pharmacology, similar results were found in relation to alcohol 
and cannabis, demonstrating that some of their properties are mediated by 
the mu system as well.  Dr Kieffer's particular interest seemed to be the 
delta receptors which she feels are related to learning, stress and even 
mood alterations such as anxiety and depression.

Much of the second part of the talk went over my head, dealing with 
sub-cellular and membrane changes, much amazingly documented visually.

A fascinating power point clip showed a 20 minute neuron clip speeded up to 
just 8 seconds showing fluorescence for delta-receptors.  In this time, 
smooth layers of visible glowing membrane-bound receptor rapidly became 
clumps of granulated intracellular material, altering the cell dramatically. 
I was told that this was not depolarisation, but a much slower response to 
other stimuli, some of which may have regulated sensitivities.  Most 
impressive of all, perhaps, were several 3-D representations of the actual 
receptor molecule with neat little indentations where opioid molecules could 
trigger pre-determined responses for depolarisation or blocking of the 
neurone involved or in some cases, movement of dopamine and other 
neuro-transmitters.  So the old 'key in lock' analogy is also valid on a 
physical molecular level!

Finally there were some questions about the fine points of her field of 
cloning, obtaining antibodies, etc.  It is always a delight to return to 
Rockefeller University in York Avenue on the East River.  Its gardens are 
quite spectacular and the modern paintings hanging in the dining area are a 
pleasure and an education.  All are on loan from the Rockefeller family 
collections (see sample below).  Dr Kreek's office has a fine view of 
Brooklyn and Queens across the elegant Queensborough Bridge.  Just three 
blocks away on York Avenue, Sotherby's Auctions were previewing some 
important French impressionist to be sold in London later in the year (see 
below).  Several had reserves over a million dollars.  The only sadness this 
year is that Dr Vincent P. Dole, aged 94, is quite unwell and no longer able 
to contribute actively to the field although he did sign the award 
certificates and send a greeting to the AATOD conference in Atlanta in 
April.

Comments by Andrew Byrne ..

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
   Dr Andrew Byrne MB BS (Syd) FAChAM (RACP)
   Dependency Medicine,
   75 Redfern Street, Redfern,
   New South Wales, 2016, Australia
   Email - ajbyrneATozemail.com.au
   Tel (61 - 2) 9319 5524  Fax 9318 0631
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Thomas De Quincey's Confessions book on free web site:
http://www.gutenberg.org/files/2040/2040-h/2040-h.htm
My grandfather Harry Gracie's letters from 1924 trip to Mayo Clinic:
http://bpresent.com/harry/code/mayo.htm
Author of: "Addict in the Family" and
"Methadone in the Treatment of Narcotic Addiction"
http://www.csdp.org/addict/
http://www.drugpolicy.org/library/byrne_contents_methadone2.cfm

AATOD Dole-Nyswander Award recipient, Atlanta 2006.




Gardens at Rockefeller University: near Flexner Hall




Composer Philip Glass by Chuck Close
On loan from the Rockefeller Family in Caspary Hall.


In return, it would appear, Philip Glass wrote "A Musical Portrait of Chuck 
Close."






These impressionist paintings were on view at Sotherby's in York Avenue near 
Rockefeller University at the time of Professor Kieffer's visit to New York.









 




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