I have said that fewer than 2% of all receptors are located at synapses,
which means that most receptors are engaged in the non-synaptic mode,
perhaps highly enriched to amplify the weak signal at sites distant from
where the transmitter is released. This arrangement of receptors means
that drugs we take act mostly through the non-synaptic channels (because
the drug distributes diffusely throughout brain tissue) and that their
psychoactive effects are therefore instructive as to what is going on in
those channels normally (without drugs). It means that most of
psychopharmacology (effects of drugs on behavior) is a study of the
non-synaptic mode. All of the hormone effects (testosterone as well as
estrogen, plus other steroids) are non-synaptic. So the bottom line is
that synaptic and non-synaptic modes are qualitatively different, and they
obviously interact.