Psychostimulants and monoamine transporters: upsetting the balance

Monoamine transporters were originally associated simply with the termination of synaptic monoamine function. In addition to amine reuptake, however, the transporters can act as ion channels that affect exocytotic neurotransmitter release and can operate in reverse mode, mediating non-exocytotic amine release. Activity at the plasma membrane is controlled by trafficking, which is modulated by interaction with both substrates and inhibitors and by cytosolic kinases and phosphatases. Monoamine transporters also constitute the principal sites of action of many psychoactive drugs, including amphetamines and cocaine, as well as therapeutic drugs for the treatment of depression, addiction and attention deficit hyperactivity disorder, each modifying the balance of presynaptic neurotransmitter function.