Noradrenergic signal transfer as a target of antidepressant therapy

Neurohormones such as norepinephrine (NE), serotonin (5-HT) and dopamine (DA) are, like hormones, informational molecules that transmit specific sets of instructions through specific membrane receptors from the outside to the inside of the cell. While research on the mode of action of antidepressant drugs has centered in the past on their effects on synthesis, release, metabolism, reuptake and hence the availability of neurohormones such as NE or 5-HT at presumptive noradrenergic and/or serotonergic receptor sites, two discoveries made during the second half of the 1970s have shifted the research emphasis on the mode of action of these drugs from acute presynaptic to delayed postsynaptic receptor mediated events. First, Vetulani and Sulser (1975) discovered that various prototypes of antidepressant treatments, including ECT, if administered on a clinically relevant time basis, decreased the neurohormonal sensitivity of the NE receptor-coupled adenylate cyclase system in brain.