Drug interactions with vesicular amine transport.

A large body of evidence has implicated monoamine neurotransmitters in a range of behavioral phenomena including mood. Reserpine depletes monoamines and induces a syndrome resembling depression (Frize 1954), giving rise to the monoamine hypothesis of affective disorders. In addition, many drugs used to treat depression act by inhibiting the reuptake of norepinephrine and serotonin from the synapse (Axelrod et al. 1961; Iversen 1976). The reinforcing properties of cocaine derive from its action to inhibit the reuptake of dopamine. Antipsychotic drugs also interfere with signaling by dopamine by interacting with dopamine receptors. Thus, extensive pharmacologic observations have implicated monoamines in psychiatric disease and drug abuse. In each case, the mechanism of drug action has revealed important features of normal signaling by monoamines, such as the role of specific receptors and transport proteins. In the case of psychostimulants, however, the specific mechanism of action remains unclear. In contrast to cocaine, which blocks the reuptake of dopamine from the synapse, amphetamines induce the release of monoamine stored within the presynaptic cell, apparently through a mechanism fundamentally different from the quantal release of classic synaptic transmission.