Why Do We Drink Coffee and Tea? 
the strength of a synapse is determined by TV, p, 
and the quantai size. There are techniques for 
measuring the quantai size directly, and a kind of 
statistical computation, known as quantai analy- 
sis, can estimate TV and p. 
We have carried out this procedure in the dentate 
neurons with either added adenosine or adenosine 
receptor antagonists. The quantai responded size 
was unaffected by any of the drugs. Quantai analysis, 
however, reveals a pronounced effect on the release 
probability: adenosine decreases and methylxan- 
thines increase the chances that a vesicle will un- 
dergo exocytosis and release its neurotransmitter 
when a nerve impulse arrives at the synapse. 
Thus methylxanthines antagonize baseline 
adenosine effects and strengthen synapses. Why 
does this act as a stimulant? About two-thirds of 
the brain's synapses are excitatory and the other 
third are inhibitory. Many drugs shift the balance 
between excitation and inhibition and thereby 
have a net stimulatory or depressive effect on the 
brain's activity. Barbiturates, alcohol, and benzo- 
diazipines (e.g., Valium) all selectively increase 
the strength of inhibitory synapses and shift the 
balance from excitation toward inhibition. We 
find that the effects of adenosine and adenosine 
antagonists on synaptic transmission are limited 
to excitatory synapses. Apparently the inhibitory 
synapses lack adenosine receptors or the second 
messenger cascades that are necessary for the ex- 
pression of their action. 
In summary, coffee and tea act (as many have 
discovered independently) as antialcohol and an- 
tibarbiturate agents, in that they shift the brain's 
excitation/inhibition balance in the excitatory di- 
rection. They do this by antagonizing the effects 
of background levels of adenosine on synaptic 
strength. Their precise mechanism of action is to 
increase the probability of release of neurotrans- 
mitter molecules from synaptic vesicles. 
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