Molecular and cellular mechanisms of antidepressant action

A long-standing theory is that brain monoamine signalling is critically involved in the mechanisms of antidepressant drug treatment. Theories on the nature of these mechanisms commenced with ideas developed in the 1960s that the drugs act simply by increasing monoamine availability in the synapse. However, this thinking has advanced remarkably in the last decade to concepts which position that antidepressant drug action on monoamine signalling is just the starting point for a complex sequence of neuroadaptive molecular and cellular changes that bring about the therapeutic effect. These changes include activation of one or more programmes of gene expression that leads to the strengthening of synaptic efficacy and connectivity, and even switching neural networks into a more immature developmental state. It is thought that through this increase in plasticity, key neural circuits within the limbic system are more easily remodelled by incoming emotionally relevant stimuli. This article attempts to bring together previous and current knowledge of antidepressant drug action on monoamine signalling at molecular and cellular levels, and introduces current thinking that these changes interact with neuropsychological processes ultimately to elevate mood.