Non-genomic effects of glucocorticoids in the neural system. Evidence, mechanisms and implications

Complementing the classical concept of genomic steroid actions, here we (i) review evidence showing that important neural effects of glucocorticoids are exerted by non-genomic mechanisms; (ii) describe known mechanisms that may underlie such effects; (iii) summarize the functions and implications of non-genomic mechanisms and (iv) outline future directions of research. The role of non-genomic mechanisms is to shape the response of the organism to challenges that require a substantial reorganization of neural and somatic functions and involve massive behavioral shifts. Non-genomic effects may (i) prepare the cell for subsequent glucocorticoid-induced genomic changes, (ii) bridge the gap between the early need of change and the delay in the expression of genomic effects and (iii) may induce specific changes that in some instances are opposite to those induced by genomic mechanisms. The latter can be explained by the fact that challenging situations require different responses in early (acute) and later (chronic) phases. Data show that non-genomic mechanisms of glucocorticoid action play a role in both pathological phenomena and the expression of ameliorative pharmacological effects. Non-genomic mechanisms that underlie many glucocorticoid-induced neural changes constitute a for long overlooked controlling factor. Despite the multitude and the variety of accumulated data, important questions remain to be answered.