New views of biogenic amine transporter function: implications for neuropsychopharmacology

Biogenic amine transporters, namely the dopamine (DA), norepinephrine (NE) and 5-hydroxytryptamine (serotonin, 5-HT) transporters (DAT, NET and 5-HTT, respectively) appear to be the key elements in regulating biogenic amine neurotransmission. These proteins therefore represent a primary target for therapeutic intervention in the treatment of numerous psychiatric disorders, such as depression, anxiety and perhaps even schizophrenia as well as drug abuse. The cloning of DAT, NET and 5-HTT and development of selective radioligands for them over the last decade has dramatically increased our understanding of their location, structure and function. These breakthroughs have also enabled remarkable progress in determining how biogenic amine transporters are regulated under not only normal conditions but also when confronted with acute or chronic exposure to a variety of stimuli including psychotherapeutic drugs. Because of the important therapeutic consequences of a better understanding of these transporters, the present review discusses recent advances in defining their mechanism of action, location and regulation and the implications of the newer data for neuropsychopharmacology.