The role of noradrenaline in depression: a review

This review summarizes some of the evidence implicating a dysfunction in the noradrenergic system in depression. Whereas the results of studies reporting changes in the concentration of the main noradrenaline metabolite, 3-methoxy-4-hydroxyphenylglycol, are equivocal, changes in adrenoceptor density and function and changes in adrenoceptors associated with the pituitary-adrenal axis function strongly implicate a disorder in central noradrenergic transmission in depression. This dysfunction may be caused by changes in the activity of tyrosine hydroxylase, the rate-limiting enzyme in the synthesis of catecholamines. The effect of corticotrophin releasing factor in modulating the activity of noradrenergic neurons in the locus coeruleus may provide the link between environmental trigger factors and central noradrenergic dysfunction. At the cellular level, evidence is presented of a link between noradrenaline and glutamate (via the N-methyl-aspartate receptor) and receptors. Such a link may provide a basis for the future development of novel antidepressants.