Mode of benzodiazepine action

[kkollins at pop3.concentric.net]

It's a bit old, but see "A GABA/Bencodiazepine Receptor Complex:
Allosteric Interactions of its Binding Sites", H. Mohler, in _Highlights
in Receptor Chemistry", Elsevier, 1984, p185ff.

Isn't the DA fx indirect?

Or you just telling me to "calm down" :-) ken collins

Dr. Alan Wheatley wrote:
> 
> This month's "Chemistry in Britain", the magazine of the Royal Society of
> Chemistry, carries an article by one of their in-house writers on drug
> addiction entitled "Drugs against drugs".  While the article is
> interesting, it seems to be at conflict with my previous understanding of
> the mode of action of benzodiazepines.  The article suggests that
> addiction results from an increase in dopamine activity:  "It is thought
> that all habit-forming drugs affect the dopamine (DA) system in the brain
> either directly as DA agonists, or by enhancing DA release, or by acting
> on other neurons responding to different neurotransmitters, which synapse
> upon this DA system to activate it."  The benzodiazepines are explicitly
> included in this explanation:  "Depressant drugs such as alcohol,
> benzodiazepines, barbiturates and opiates virtually all act on the
> gamma-aminobutyric acid (GABA) inhibitory neurotransmitter system.  These
> substances indirectly affect the DA system by lowering the threshold of
> its activation."  There is an accompanying diagram, showing a GABAergic
> neuron synapsing directly onto a dopaminergic neuron.  When I last had
> reason to consider this matter, several years ago, the prevailing view was
> that the principal action of benzodiazepines was the production of
> inhibitory GABA-like effects that led to a reduced turnover of monoamines
> in the brain.  Does that view still hold?  If so, are the quotes from the
> article simply wrong, or do the benzodiazepines come within the category
> "acting on other neurons responding to different neurotransmitters, which
> synapse upon this DA system to activate it"?  I should welcome any light
> that can be thrown on this apparent discrepancy, please.
> 
> Dr. Alan Wheatley at www.canadalane.demon.co.uk