Antidepressants and Morphological Plasticity of Monoamine Neurons

In the 1950s, the monoamines 5-hydroxytryptamine (5-HT) (Woolley & Shaw, 1954), noradrenaline (NA) (Vogt, 1954), and dopamine (DA) (Carlsson, 1958) were identified in the brain. After this discovery, it was identified that the tricyclic compound imipramine and the antituberculosis drug iproniazid were effective in the treatment of clinical depression, and that these drugs can increase the extracellular concentration of monoamines by inhibiting the re-uptake of 5-HT and NA and by blocking monoamine oxidase (MAO) respectively. These findings have led to the catecholamine hypothesis of depression (Schildkraut, 1965), followed by the monoamine hypothesis (Coppen, 1967), which propose that depression is caused by deficiencies within the central catecholaminergic or monoaminergic systems respectively. At present, it is understood that all antidepressants increase monoamine levels in the brain. Other evidence supporting the monoamine hypothesis has also been put forward: reserpine, which depletes monoamines in the synaptic cleft, caused depressive symptoms in some patients taking it for the treatment of hypertension. 5-HIAA, the primary metabolite of 5-HT, was seen as reduced in the cerebrospinal fluid of clinically depressed patients. All these findings suggest that monoamine concentrations in the brain are reduced in depressive patients.