Help needed: chemistry of alcohol addiction

Mike Kirby mkirby at vt.edu
Sat Mar 23 17:21:05 EST 1996

Martin Auer <100571.2073 at compuserve.com> wrote:

> Please help. I'm writing a book in which an alcoholic appears. Now I need 
> to know what exactly happens in the body when a person drinks alcohol. 
> What is the chemistry of it? Why is it addictive? Because of a similarity 
> with some other substance the body really needs? Could addiction be 
> described as a sort of "chemical misunderstanding"? How does addiction 
> change the metabolism so that the body _needs_ alcohol after a while? Is 
> there a general theory of addiction?


Any basic toxicology text will provide specific information for you. 
Here's an answer which I hope can be understood by the layperson...  

Ethanol (EtOH) functions in the CNS as a GABA-A agonist.  That is, EtOH
augments the binding of GABA (gamma-aminobutyric acid) to GABA-A
receptors, which possess an endogenous Cl- (chloride) channel.  Prolonged
GABA-A stimulation, under moderate concentrations of GABA (vs. very high
concentrations which can result in excitatory responses) will reduce the
probability of generating an action potential in the target neuron.  In
other words, GABA depresses the neurotransmitter output of the target
cell.  Regarding addiction, recent work in pharmacology suggests that the
gross effect of EtOH on the brain results in higher dopamine output in the
nigrostriatal tract (dopamine neurons which project from the substantia
nigra pars compacta to the striatum [caudate nucleus and putamen]) and the
medial forebrain bundles.  Increased dopaminergic stimulation causes
pleasure-enhancing effects (this is similar to the way in which cocaine
operates; cocaine blocks dopamine uptake and increases the amount of
synaptic dopamine available to dopamine receptors).  Addiction results
from both a psychological need to experience the desired state and
alterations in receptor kinetics (rate of operation) or expression in
cells.  Metabolism of EtOH primarily takes place in the intestinal tract
(some), the liver (mostly), and in the bloodstream.  Also, the body will
make adjustments to increase excretion of EtOH.  The particular class of
mixed function oxidases (MFO or p450) induced (meaning increased in
number) by EtOH also will metabolize many other substances, including
drugs which complicate attempts at drug therapy for diseases in
alcoholics.  Your 'tolerance' to EtOH is mainly a result of protection by
liver enzymes (MFOs), which if the liver is stressed for prolonged periods
will lead to cirrhosis.  Hope this helps.

Mike Kirby

Mike Kirby

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